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Press Release

Press release

New hiv drug can only offer hope of ending aids if all have access, unaids says.

GENEVA, 10 July 2024— UNAIDS has welcomed the release of Gilead Sciences’ t

GENEVA, 10 July 2024— UNAIDS has welcomed the release of Gilead Sciences’ trial results on the injectable long-acting HIV medicine Lenacapavir for HIV prevention. The result “provides hope of accelerating efforts to end AIDS”, UNAIDS says, “but only if Gilead ensures that all people who need it can have access to this game-changing medicine.”

The recent trial of the medicine among cis-gender women in Uganda and South Africa was so successful that it was halted early. Twice-yearly injections of Lenacapavir showed overwhelming efficacy for preventing HIV infections compared to standard oral preventative HIV medicines, known as pre-exposure prophylaxis (PrEP). Additional trials are ongoing in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States.

UNAIDS has welcomed the “exciting development,” and urged the company to allow generic production of Lenacapavir to all low- and middle-income countries by negotiating voluntary licensing agreements through the Medicines Patent Pool (MPP). The MPP is a UN-backed programme with extensive experience negotiating generics agreements between originators and generic pharmaceutical companies.

Gilead has not yet announced its plans for low and middle-income countries. However, UNAIDS is concerned that Gilead’s latest statement regarding its access strategy for low and middle-income countries mentions only “high incidence countries and resource limited countries” and makes no specific mention of upper-middle-income countries or the Medicines Patent Pool. Upper middle-income countries account for 41% of new HIV infections and 37% of all people living with HIV. These countries are home to millions who cannot afford the prices Gilead charges high-income countries.

“The success of Gilead’s recent Lenacapavir trial is an exciting development. While we still await regulatory approvals, normative guidance and results from the other ongoing trials, this news offers hope that we can enable everyone who would benefit, including especially the most marginalised communities, to have access to the help they need. Enabling equitable global access to new technologies can help get the world on track to end AIDS as a public health threat by 2030,” said Winnie Byanyima, Executive Director of UNAIDS. "However, it is concerning that Gilead’s latest announcement seems to mention neither upper-middle income countries, where people cannot afford anything like Lenacapavir’s current $42,250 price tag, nor a commitment to work with the UN-backed Medicines Patent Pool. Without these safeguards, it cannot be assured that this game-changing medicine will reach all those who need it."

Data in this press release comes from UNAIDS 2023 Epidemiological estimates (aidsinfo.unaids.org)

The UNAIDS Executive Director joined more than 300 experts and activists calling for a generic version of Lenacapavir to be licensed to all low and middle-income countries through the MPP, in a letter coordinated by the People’s Medicines Alliance: https://peoplesmedicines.org/wp-content/uploads/2024/05/Gilead-Open-Letter_May-2024.pdf

The AIDS Vaccine Advocacy Coalition provides an overview of the Lenacapavir for PrEP trials: https://avac.org/resource/infographic/an-overview-of-lenacapavir-for-prep-trials/  

The Joint United Nations Programme on HIV/AIDS (UNAIDS) leads and inspires the world to achieve its shared vision of zero new HIV infections, zero discrimination and zero AIDS-related deaths. UNAIDS unites the efforts of 11 UN organizations—UNHCR, UNICEF, WFP, UNDP, UNFPA, UNODC, UN Women, ILO, UNESCO, WHO and the World Bank—and works closely with global and national partners towards ending the AIDS epidemic by 2030 as part of the Sustainable Development Goals. Learn more at unaids.org and connect with us on Facebook , Twitter , Instagram and YouTube .

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Aids 2024 — exciting developments with the jabs promising to revolutionise HIV prevention

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Arguably, the biggest HIV news of the year so far broke at the end of June when it was reported that an injection containing the antiretroviral drug Lenacapavir provides young women and adolescents with six months of highly effective protection against HIV infection per jab.

Dr Nkosiphile Ndlovu, a senior research clinician in the Clinical Trials Division of the Wits Reproductive Health and HIV Institute Research Centre, pointed out that there are two registrational trials looking at the Lenacapavir injection for HIV prevention. The one in young women and adolescents that was just reported is called PURPOSE 1. PURPOSE 2, a similar study conducted in men, transgender people and gender non-binary individuals who have sex with men, is ongoing. Ndlovu was involved in PURPOSE 1.

Mitchell Warren, executive director of a US-based HIV advocacy group, the Aids Vaccine Advocacy Coalition, told Spotlight results from PURPOSE 2 are expected late in 2024 or early in 2025. If these results show that Lenacapavir as injectable HIV prevention given every six months is safe and effective, Gilead will go to regulators and the World Health Organization (WHO) to have the product approved for use. In South Africa, Gilead will have to apply for registration with the South African Health Products Regulatory Authority.

But when and on what terms generic manufacturers will be allowed to produce the Lenacapavir jab remains uncertain.

Gilead previously told Spotlight it would follow a “direct voluntary licensing strategy for access to Lenacapavir in high-incidence, resource-limited countries”. We understand this to mean it will make licensing deals directly with generic companies, rather than through an intermediary such as the UN-backed Medicines Patent Pool (MPP). But Gilead is under substantial pressure to change course. Most recently, in a strongly worded statement , UNAIDS urged Gilead to work through the MPP.

Even if licenses are granted very quickly, directly or via the MPP, it is likely to take several years before generic companies can produce Lenacapavir jabs.

Spoiled for choice? What's blocking uptake of HIV prevention tools

Prevention champions: gpc country-support teams strengthening stewardship for hiv prevention programmes, long-acting injectable lenacapavir proves effective in hiv prevention for women.

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HIV/AIDS: Current Updates on the Disease, Treatment and Prevention

Praveen kumar gupta.

Department of Biotechnology, R.V College of Engineering, Bangalore, 560059 India

Apoorva Saxena

CCR5-delta 32 homozygous stem cell transplantation for HIV-infected individuals is being treated as a milestone in the global AIDS epidemic. Since 2008, when the second Berlin patient was cured from HIV after undergoing transplantation from a donor with delta-32 mutation, scientists are aiming for a long-term cure for the wider population. In 2019, a London patient became the second person to be free of HIV and came off the antiretroviral drugs completely. CCR5 gene is now being treated as a viable target for HIV treatment. It can be used in the treatment of HIV either through administration of drugs that bind to CCR5 and stop the receptor from working or through gene therapy to alter the CCR5 gene using CRISPR/Cas9 and prevent protein production. This review article aims to identify the obstacles and the need to overcome them in order to bridge the gap between current research and future potential cures for HIV.

Introduction

Human immunodeficiency virus or HIV is the cause of HIV infection that leads to the autoimmune disorder acquired immune deficiency syndrome (AIDS) [ 1 ] (Fig.  1 ). The major cause of spreading of HIV is through unprotected sex, during pregnancy from mother to foetus, through contaminated hypodermic needles and infected blood transfusions [ 1 ]. In the year 2016, an estimated 37 million people were living with HIV and 1 million deaths were reported. HIV/AIDS is a pandemic condition—an epidemic of diseases that spreads across large areas like multiple continents or even worldwide [ 1 ]. The first time AIDS was recognized was in the year 1981 by the United States Center for Disease Control and Prevention (CDC). Since the reported case of an individual who had successfully undergone a stem cell transplant from a person who showed a homozygous CCR5-delta 32 mutation, after receiving extensive high dose chemotherapy, there has been a greater interest in finding a potential cure.

Human Immunodeficiency Virus [ 5 ]

HIV is a type of retrovirus that adversely infects the immune system of a human, mainly targeting the CD4 + T-helper cells, accessory cells and the macrophages [ 2 ]. When it gains entry into the target cell, the viral genomic RNA undergoes a process of the reverse transcription with the help of reverse transcriptase enzyme and forms double stranded DNA (ds-DNA). This ds-DNA then gets integrated into the target cellular DNA with the help of enzyme integrase and other host co-factors [ 3 ]. The virus now can either become dormant or conceal itself and the target cell detection by the host immune system or it can get transcribed into new viral RNA and proteins that are released from the cell and begin the cycle again. HIV can be characterized into 2 major classes—HIV-1 and HIV-2. HIV-1, which is more virulent, infective and the major cause of HIV in humans, was discovered first and was initially referred to as HTLV-III or LAV [ 4 ] (Fig.  2 ). HIV-2 is less infective and far fewer people exposed to it are infected.

Structure of HIV-1 [ 8 ]

The crucial factor in gaining entry into target cell is through binding of HIV to the CD4 receptor present on the T-helper cells and to one of the chemokine receptors- either CCR5 or CXCR4 [ 6 , 7 ]. Binding to the co-receptor depends on the virus’s tropism which is the ability to bind to a specific receptor. Naturally, there are two types of tropic strains—R5 that bind to CCR5 and X4 which bind to CXCR4. Dual tropic strains are capable of binding to both. Of these two co-receptors, CCR5 is the prime receptor for virus’s entry into the target cell. R5-tropic strains prevail during early stages of infection, whereas the X4-tropic strains emerge later with disease progression. The envelope-like glycoprotein structure of HIV-1 is paramount in ensuring the viral entry into a target host cell [ 7 ]. This glycoprotein has 2 protein subunits: the gp41 (transmembrane) subunit and gp120 (external) subunit, which mimics a chemokine [ 6 , 7 ]. It does not manifest the unique structure of the chemokine but somehow manages to bind to both the co-receptors [ 6 ]. It forms a heterotrimeric complex wherein the gp120 subunit binds to the CD4 protein and specific co-receptor present on the target cell [ 6 ]. When this complex is formed, it triggers the release of a peptide which facilitates cell–cell fusion, that causes the viral membrane to fuse with the target cell membrane [ 6 ]. Binding to CD4 alone is not sufficient as it can result in gp120 shedding. So, it has to bind to the specific co-receptor for the fusion to proceed. The V1–V2 region of gp120 is recognized by the co-receptor, that influences which co-receptor will bind to the protein and is determined by degree of N-linked glycosylation and peptide composition. The highly variable V3 loop is the one that determines co-receptor specificity. The binding of gp120 glycoprotein to the CCR5 co-receptor is determined by two essential factors—the tyrosine-sulphated amino terminus of CCR5 receptor and following which there must be reciprocal action between the transmembrane domains of CCR5 and gp120 protein, i.e., inter-communication and synergy.

Antiretroviral Therapy

The usage of a combination of three or more antiretroviral drugs for suppression of the HIV infection is called antiretroviral therapy. Using multiple drugs in combination to increase the effectivity on various viral targets is called highly active antiretroviral therapy (HAART). It helps in maintaining the immune system to function, preventing HIV from developing resistance and other infections that potentially lead to death. The five classes of drugs used in combination to treat HIV infection are: entry inhibitors, nucleoside/nucleotide reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase inhibitors and protease inhibitors.

Zidovudine/ZVD (also called azidothymidine) is an extensively used antiretroviral medication [ 9 ]. It is a thymidine analogue and is dosed twice daily in combination with other antiretrovirals. Its function is to particularly inhibit the reverse transcriptase enzyme which is necessary for the production of ds-DNA.

Cellular enzymes are used in converting AZT into the 5′-triphosphate form. Research studies suggest that the termination of forming ds-DNA chains is a crucial factor that leads to an inhibitory effect.

Studies have also shown that at very high dosage of this drug, its triphosphate form may inhibit the DNA polymerase enzyme which is used for cell division by the uninfected cells and mitochondria for replication. It may lead to toxic but reversible effects on certain skeletal and the cardiac muscles, causing the condition of myositis [ 10 ]. However, zidovudine also shows greater affinity for the reverse transcriptase enzyme, which is around 100-fold. This selectivity has been proven by the cell's ability to quickly repair its DNA strands if broken by AZT during its formation, whereas the HIV virus will lack this ability (Fig.  3 ).

Structure of zidovudine [ 11 ]

Zidovudine is commonly used in combination with nucleotide reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, HIV integrase strand transfer inhibitor and protease inhibitor [ 9 ]. The combination of lamivudine and zidovudine is not recommended for non-pregnant HIV-infected adults and adolescents due to greater toxicity but is used as an alternative, though not a preferred one, in antiretroviral-naive pregnant women as an initial treatment [ 9 ]. However, for paediatric patients (neonates, infants and children of age 12 or less), zidovudine with lamivudine/emtricitabine is a preferred option. For adolescents greater than the age of 12, it is an alternative [ 9 ].

Zidovudine Administration and Pharmacokinetics

Administration and dosage.

It is usually administered orally or by continuous IV infusion, although not rapid infusion and IM injection [ 9 ] (Tables ​ (Tables1, 1 , ​ ,2). 2 ). The dosage for paediatric patients and adult patients depends on their body weight (Tables ​ (Tables3, 3 , ​ ,4 4 ).

Oral administration [ 9 ]

IV administration [ 9 ]

Dosage for paediatric patients [ 9 ]

Dosage for adult patients [ 9 ]

Administration

Zidovudine: 1 mg/kg every 4 h [ 9 ].

Pharmacokinetics

Pharmacokinetics gives a detailed view of the fate of drugs in the human system. It includes various components like absorption, distribution, excretion or elimination and metabolism (Tables ​ (Tables5, 5 , ​ ,6, 6 , ​ ,7). 7 ). The stability of such retroviral drugs should also be taken into account for both oral and parenteral dosage forms (Table ​ (Table8 8 ).

Absorption [ 9 ]

Distribution [ 9 ]

Elimination process [ 9 ]

Stability of antiretrovirals [ 9 ]

Contraindications [ 9 ]

• Zidovudine has a history of life-threatening hypersensitivity reactions like Stevens–Johnson syndrome and anaphylaxis to the drug or maybe due to some ingredient in the formulation.
• Lamivudine/zidovudine: hypersensitivity history.
• Abacavir/zidovudine/lamivudine: history of hypersensitivity to abacavir, zidovudine or lamivudine; hepatic impairments may be mild or severe.

CCR5 Gene Structure

C–C chemokine receptor type 5 (also called CCR5 or CD195) is a receptor for chemokines present on the white blood cells. The CCR5 gene in humans is located on the short arm (p) at position 21 on chromosome number 3 (Fig.  4 ). It is mainly expressed cells like T-cells, macrophages, microglia, dendritic cells and eosinophils and is found within a cluster of genes coding for some other receptors like XCR1, CCBP2, etc. [ 12 , 13 ]. The gene has two promoters, three exons and two introns. Pu or PR2, the upstream promoter, has a 1.9 kb region, 57 bp in length and precedes the exon 1 [ 12 ]. Exon 1, which is the start of the coding region, is followed by the first intron, 501 bp in length. The second exon 2 is intron-less. It is found as exon 2a, 235 bp in length, and exon 2b, 54 bp in length. Pd or PR1, the second promoter, accommodates the intron 1 and exon 2 regions [ 12 ]. A 1.9 kb length intron is located between exon 2 and exon 3. Exon 3 is also intron-less and consists of the full ORF of the CCR5 gene, 11 bp of the 5′ untranslated regions and the complete 3′ untranslated regions [ 12 ].

Location of CCR5 gene on chromosome 21 [ 14 ]

These two promoters are devoid of the consensus TATA and CCAAT sequences, although the Pd promoter has a non-consensus TATA sequence and have an unusually high content of pyrimidine in them [ 12 ]. The upstream Pu promoter was found to be weaker than the downstream Pd promoter which had exhibited up to fivefold greater activity. But these results were established as erroneous [ 13 ]. With the help of RT-PCR technique, it was later identified that the Pu promoter was used in stimulated T-cells and the Pd promoter was used in unstimulated primary T-cells [ 13 ]. The error resulted due to the use of transformed T-cells affecting the overall expression of CCR5 protein via the Pu promoter [ 13 ]. Results also showed that transcription of the CCR5 gene when controlled by the Pu promoter containing exon 1 resulted in CCR5A or B and when controlled by the Pd promoter resulted in truncated isoforms [ 13 ].

CCR5 Gene Expression Regulation

The expression of CCR5 gene is regulated at three levels: 1. genetic factors, 2. factors involved in activation, signalling and trafficking of the receptor which includes desensitization, internalization and recycling and 3. environmental triggers [ 13 ].

CCR5 receptor is part of the G-protein coupled receptor family, which binds to its ligand and releases αi and βγ G-protein subunits. This results in a mediated effector response. Such responses stimulate the release of phospholipase Cβ and adenylyl cyclase. This in turn facilitates the release of intracellular calcium and form inositol triphosphate [ 13 ]. This leads to activation of phosphorylation of the CCR5 receptor which occurs at the serine and C-terminal residues via protein kinase C and G-protein coupled receptor kinases [ 13 ]. The regulatory proteins, β-arrestin 1 and 2, bind to the activated serine and the conserved DRY motif in the intracellular loop [ 13 ]. The β-arrestin proteins have functions like desensitizing the receptor to further stimulation and participating in endocytosis. The CCR5 expression level is controlled by the rates of recycling and endocytosis [ 13 ]. In the endocytosis process, β-arrestin protein facilitates the binding process between clathrin-coated pits and the phosphorylated receptor. Infection and entry of HIV into cells do not require CCR5 signalling, but the chemokine-induced endocytosis decreases the available receptor for HIV entry. This is the process of chemokine-mediated anti-HIV activity [ 13 ].

Environmental factors affecting CCR5 expression are infectious pathogenic agents like Mycobacterium tuberculosis , which increases the CCR5 expression. Studies have shown that CCR5 expression is considerably increased in all leukocyte subset cells during tuberculosis and dual infection with HIV [ 13 ]. However, the level of CCR5 expression on CD4 + T-cells was not increased. Conversely, it was also shown that HIV affects the level of expression of CCR5, due to a correlation with HIV disease progression. Individuals with end stage HIV were shown to have the highest percentages of CCR5 expressing CD4 + T-cells [ 13 ].

The regulation of CCR5 is complex. The introns as well as sequences in the 5′ UTR and 3′ UTR affect CCR5 gene regulation [ 13 ]. Therefore, mutations in these regions should be considered critical in the regulation process.

CCR5-Delta 32 Mutation

The discovery of CCR5-delta 32 mutation in the CCR5 gene in 1996 which exhibited some protection against HIV was a ground breaking one. Studies showed that the CD4 + T-cells when expressing this mutation prevented HIV envelope fusion [ 12 ] (Fig.  5 ). The mutant allele has a length of 215 in comparison to the wild type which contains 352 amino acid residues [ 13 ]. This mutation basically results due to the deletion of 32 base pairs from the position of nucleotides starting from 794 till 825, a frameshift mutation, and seven new amino acids are incorporated between amino acid 174 and stop codon at amino acid 182 [ 13 ] (Fig.  6 ). This mutation affects the region of second extracellular loop where the resultant protein lacked the last three transmembrane domains and also some regions necessary for G-protein interaction and signal transduction.

Comparison of HIV infecting cell with CCR5 and without CCR5 [ 15 ]

Difference between wild type CCR5 and CCR5-delta 32 [ 16 ]

This mutation is majorly restricted to people of European descent. The gene frequencies are found to be around 10% and shows a decline from north to south latitude. A 2–5% gene frequency in Europe, the Middle East and parts of the Indian subcontinent was observed in more than 3000 individuals. The highest frequency, at 20.93%, was discovered in the Ashkenazi Jewish population. The mutant allele is absent in Black populations excluding the African American group who may have acquired the mutation through genetic admixture [ 13 ].

The origin of the delta-32 mutant allele has been dated back to the year 275–1875, which increased over a period of time as a result of selective pressure, mainly the Black plague. However, historical data have shown that Black plague may not in fact be the cause [ 13 ]. The distribution of the delta-32 mutant allele in a north to south gradient does not correlate to the casualties of the plague and instead follows a south to the north gradient. The Black plague has shown the greatest casualties in areas like the Mediterranean region and China, with lowest allele frequencies of the mutation [ 13 ].

Studies suggested that delta-32 arose without a selective event. Tandem repeats found in the coding region of the CCR5 gene could cause unequal homologous recombination, which results in the delta-32 allele. The origins of the delta-32 mutation, however, remain a mystery [ 13 ].

The hype about the delta-32 mutation comes from its ability to protect homozygous individuals from HIV. The protective effect of the delta-32 mutation is a result of eliminating the expression of CCR5 protein on the cell surface, which prevents HIV’s entry into the cell. In the year 1997, however, studies showed that some of them having the homozygous delta-32 mutation were HIV-infected [ 13 ]. Further studies revealed the HIV virus was of the X4 type, which led to very rapid CD4 + T cell decline. Hence, this mutation is limited in its function and does not protect against viral strains which utilize other receptors or show dual-tropism [ 13 ].

In contrast, however, the delta-32 protein product which is localized to the endoplasmic reticulum is an important factor. It is shown to exert a trans-dominant negative effect on the wild-type CCR5 protein, which inhibits its transport to the cell surface. Further analysis in vitro showed the reduction of surface expression of wild type CCR5 and CXCR4 through dimerization by this mutant protein product [ 13 ]. This confers an inhibition to R5, X4 and R5X4 HIV infections [ 13 ]. Homozygous delta-32 individuals with this mutant protein were shown to have suppressed CXCR4 surface protein expression and decreased susceptibility to X4 infection. Experimental proofs also suggested that delta-32 heterozygous individuals with HIV infection do not stably express the mutant protein, are devoid of the molecular mechanism of complete protection and only maybe partially protected [ 13 ].

Stem Cell Transplantation

Stem cells are undifferentiated cells that can differentiate into specialized cells and can also undergo mitosis to produce more stem cells. There are mainly two classes—embryonic stem cells (ECS) and adult stem cells. Stem cells are also taken from the umbilical cord blood just after birth. These act as a repair mechanism for the body, such as skin, blood or intestinal tissues. Adult stem cells are majorly used in medical therapies like bone marrow transplantation. Bone marrow is the spongy tissue present inside the bones which serves as a rich source of adult stem cells. Long-term control of HIV is possible with CCR5-delta 32 stem cell transplantation [ 13 ].

Allogeneic transplantation of stem cells with this mutation in patients with HIV infection and malignancy has been considered as an option since the late 1990s (Fig.  7 ). Human leukocyte antigen (HLA) is a critical factor to be considered during the process of transplantation. The HLA should be a proper match; otherwise, it would lead to rejection by the recipient’s immune system. The limited availability of HLA-matched unrelated donors has made it even more difficult. Only about 1% of Caucasians possess this CCR5 null allele [ 13 ].

Allogeneic hematopoietic stem cell transplant [ 17 ]

Gene Therapy

Zinc finger nuclease technology is a popular tool which can be used for targeting specific DNA sequences in the genome. It falls in the class of restriction enzymes and is artificially made by fusing a zinc finger DNA-binding domain and DNA-cleavage domain. This technique is also engineered to eliminate the CCR5 expression over CD4 + T-cells, and the modified cells have shown to have a half-life of 48 weeks [ 13 ]. But it has its own issues. It is difficult to ensure that the desired repair mechanism is one which is used to repair the double stranded break (DBS) [ 13 ]. It is also challenging to scale it upwards and is an expensive technique.

A breakthrough technique, the CRISPR/Cas9 gene-editing system, is also used to eliminate the CCR5 receptor on the blood stem cells which can give rise to differentiated blood cells that are devoid of this receptor [ 18 ] (Fig.  8 ). These gene-edited stem cells can be established into an HIV-infected patient through bone marrow transplantation and give rise to an HIV-resistant immune system [ 18 ]. This technique, however, can also go sideways which leads to unwanted results that can cause ethical issues to rise. As seen in the highly controversial case of the Chinese scientist, He Jiankui, who with the help of this technology deleted the CCR5 gene in the twins, Lulu and Nana, introduced some unintended mutations in their genetic codes. There is still a lot of research needed to make this technology bioethically a safe tool.

CRISPR/Cas9 gene editing [ 19 ]

Researchers have also engineered a molecule called the chimeric antigen receptor (CAR) and introduced a gene for that molecule into blood-forming stem cells [ 18 ]. This molecule has two receptors that will recognize the antigen (HIV) and direct the immune cells to locate and kill the HIV-infected cells [ 18 ]. When transplanted into mice, which would have the CAR-carrying blood stem cells, it would result in reduced levels of HIV by inducing the immune cells to fight effectively against the virus [ 18 ]. An 80% to 95% drop in viral load was observed in the mice [ 18 ]. It was concluded that gene therapy could be a feasible option for treatment in HIV-positive humans.

Immunological Approaches

Studies have shown that vaccine can contribute effectively in viral clearance such as the Rhesus CMV vaccine vector [ 18 ]. A vaccine vector is a kind of vaccine which consists of chemically weakened viruses that are transported in the body to generate an immune response. The genes used in these vaccines are antigen coding surface proteins from that particular pathogen.

SAV001-H is the first and only preventive HIV vaccine which uses killed HIV-1 virus [ 18 ]. It is unique from other vaccines, as it uses genetically engineered whole virus genome, eliminating its pathogenicity and inactivating its virulence through irradiation and chemical treatments, finally approaching to the first “whole-killed virus”-based HIV vaccine [ 18 ]. The results of Phase 1 clinical trial, which were completed in the year 2013, were found to have serious and adverse effects in the 33 participants [ 18 ]. There was also a surprising boost in the antibody production against p24 and gp120. The HIV viral core is mostly made up of the structural protein, p24, which is called the capsid. A crucial factor in the diagnosis of primary HIV-infected individuals is the p24 antigen assay. High levels of p24 are found in the blood serum during the period between infection and seroconversion. The antibody production is found to increase as much as 64-fold [ 18 ]. The antibody production against gp120, which is a glycoprotein, necessary for attachment to a cell receptor and allow HIV entry, is found to increase up to eight-fold [ 18 ].

Another promising vaccine called the Kang's vaccine also uses the “whole-killed HIV-1,” which is similar to vaccines developed for rabies, polio and influenza [ 18 ]. However, HIV-1 is genetically engineered in such vaccines and raises questions about safety and possibility of large quantity production.

Researchers have also tested an immunogen called eOD-GT8 60mer, a protein nanoparticle, which is designed to mimic a crucial part of the HIV envelope protein which will bind to and activate the B cells to produce plasma cells that secrete antibodies needed to fight HIV [ 18 ]. This nanoparticle was developed in the Schief laboratory and tested in mouse models engineered by the Nemazee laboratory [ 18 ]. The researchers showed that immunization with eOD-GT8 60mer produced antibody progenitors with some of the characters crucial to recognize and block the HIV infection, proposing that it could be a promising first step in a series of immunizations against HIV [ 18 ]. The vaccine appears to work well in mouse models. The researchers are now investigating other immunogens that could work in coexistence with eOD-GT8 60mer [ 18 ].

Case Studies

The berlin patient [ 20 ].

The strongest proof available in favour of a HIV cure stems from the case of Timothy Brown who is popularly known as the Berlin patient (Fig.  9 ). He is considered the first person ever to be cured of HIV. The victory was predicated on doctors taking advantage of nature’s own experiment—the genetic mutation of CCR5 gene that produces a protein co-receptor present on the surface of CD4 + T-cells that HIV uses to gain entry. He was attending university in Berlin when was diagnosed HIV positive. His initial treatment include ART, and he was taking low doses of zidovudine and protease inhibitors. He continued to live a normal life for the next 10 years. But one day, he was again feeling extremely exhausted and the doctor had diagnosed it to be anaemia. He had received red blood cell transfusion for nearly a week and was then sent to an oncologist, Dr Huetter, when the previous doctor was unable to resolve the situation. The oncologist performed a painful bone marrow biopsy and after further diagnosis he was informed that he had acute myeloid leukaemia (AML).

Timothy Ray Brown a.k.a. “The Berlin patient” [ 21 ]

He then started receiving treatment at one of the Berlin University hospitals and had to receive four rounds of chemotherapy treatment. During the third round of chemotherapy, he had gotten a fatally dangerous infection and was immediately put into an induced coma. His blood sample was collected and sent to a stem cell donor bank with the German Red Cross to find matches in case he needed transplantation. Luckily, he had 267 matches which sparked an idea to locate donors with a homozygous CCR5 delta-32 mutation on CD4 + T-cells who are almost immune to HIV infection. A donor was found at the 61st attempt and had agreed to donate when necessary (Fig.  10 ).

Adam Castillejo a.k.a “The London patient” [ 23 ]

However, Timothy Brown had been reluctant and had said no to transplantation as the success rate was only 50–50. But at the end of 2006, leukaemia had rebounded and he desperately needed transplantation to survive. He received the stem cell transplant on February 6, 2007 and stopped taking his antiretroviral medication. Nearly 3 months after he underwent transplantation, HIV was no longer found in his body and he had thrived until the end of the year.

Unfortunately, life had other plans for him. After coming back from a trip to the USA, he was diagnosed with pneumonia and the leukaemia was back. The doctors decided to treat him with a second transplantation from the same donor in February 2008. The recovery was a tough one. He was almost paralyzed and went nearly blind. He had, however, eventually learnt to walk again and fully recovered 6 years later. He was continuously tested for HIV with extensive and precise tests. It was finally good news for him! Since 2010, when he decided to go public, he had interviewed for various magazines: POZ Magazine , New York Magazine and Science Magazine among others and decided to devote his life in supporting research for cures against HIV. In July 2012, he started the Timothy Ray Brown Foundation under World AIDS Institute and has worked with many scientists, organizations, research laboratories and universities to work on cures such as vaccination against HIV.

The London Patient [ 22 ]

The London patient may be the second person with HIV to no longer have the virus. In March 2019, in a report published in journal Nature , a group of investigators had announced the cure of a second HIV-positive patient. His success story depicts that CCR5 is a viable target for HIV research and treatment.

The London patient, who had chosen to remain anonymous, came out in public on March 9 th 2020. Adam Castillejo grew up in Caracas, Venezuela, and later shifted to London with his mother, as his parents were divorced. He was first diagnosed with HIV in 2003 and had started taking drugs to control the HIV infection in 2012. He had taken antiretroviral therapy for years before being diagnosed with an advanced form of blood cancer called Hodgkin’s lymphoma. Again, as in the case of the Berlin patient, the cancer was resistant to standard chemotherapy, so his doctors had advised more intensive chemotherapy along with bone marrow stem cell transplant. In 2016, he had agreed to transplantation and received it from a healthy donor who carried the CCR5 mutation. So, when his immune system regrew, it lacked the protein and was impervious to HIV. His virologist, Dr Ravindra Gupta, from the University of Cambridge, thinks it is a cure because a year had passed and they had carried out a few more tests for the viral load. In Adam Castillejo’s own words, “I don’t want people to think, “Oh, you’ve been chosen.” No, it just happened. I was in the right place, probably at the time right time, when it happened.” Adam Castillejo wants to be the “ambassador of hope” for people with this illness.

Although the scientists describe this case as a long-term remission, experts are calling it a potential cure. Such transplants are, however, dangerous and can be fatal. They are also an impractical approach to cure the millions already infected. These are highly risky procedures and can lead to serious complications. There still has to be a lot of research done to extend this type of treatment to a wider population infected with HIV.

A comparative study of the two patients reveals that their cases were in fact quite similar (Table ​ (Table9 9 ).

Summary of the two cases—the Berlin patient and the London patient [ 24 ]

Lifestyle Practices to Prevent HIV Infection

Prevention is better than cure. And with HIV infections, one should practice prevention with utmost care and sincerity. An HIV diagnosis could turn one’s life upside down. So, it’s better to lead a healthy lifestyle by making the correct choices.

Measures for Protection Against HIV Infection

HIV is majorly spread through unprotected vaginal or anal sex. Choose less risky behaviour and be cautious. Not taking medicines to prevent or treat HIV is equally responsible for HIV infection. The number of sexual partners should be limited. One should get tested for sexually transmitted diseases and also know the sexual partner’s status. One can talk about pre-exposure prophylaxis to their respective healthcare provider. It is a preventive option for people who are not infected yet but are exposed to high risks of being HIV positive. HIV is also spread through intravenous injections and blood transfusions. Use of sterile equipment in such cases is a necessity.

Pre-exposure Prophylaxis

This is a preventive method of taking pills by people who are not HIV positive yet but who are at a high risk of getting infected and spreading it to others. A pill, named Truvada, contains two medicinal components, emtricitabine and tenofovir, that are used in combination with other drugs to treat HIV [ 25 ]. These medicines work on keeping the virus from creating a permanent infection.

Post-exposure Prophylaxis

Post-exposure prophylaxis (PEP) is a short course of HIV medicines taken soon after a possible exposure to HIV [ 25 ]. Every hour counts. For the treatment to be effective, the course should begin within 72 h after exposure to HIV; otherwise, it will not have any effect [ 25 ]. This treatment should be used only in cases of emergency. A person prescribed with PEP will need to take the medicines for 28 days at a stretch and then visit their respective healthcare provider for further tests [ 25 ]. Even if taken correctly, it may not be 100% effective. The sooner the medication is started, the better.

Healthy Practices to Follow When Living with HIV

A healthy, well-balanced and nutritious diet can help a person lead a better life by preventing health related issues like malnutrition and stopping the progression from HIV to AIDS. A well-balance diet is rich in whole grains, fresh fruits and vegetables, protein, low fat dairy products and multivitamins like zinc and B12. It also constitutes what should be cut down—fried foods, processed foods and sugary drinks. Smoking should be stopped when diagnosed with HIV. According to CDC, in the USA, the rate of adults with HIV, smoking is two to three times higher in adults infected with HIV than the nearly 18% of uninfected adults who smoke. Researchers at the Syracuse University analysed the data from 212 adults infected with HIV and found that the ones who smoked reported having more symptoms like dizziness and coughing.

Putting a stop to illegal drug use is equally necessary. People should seek treatment for addiction to illegal drugs like heroin, cocaine and methamphetamines. Sharing of needles for drugs can leave one exposed to other infections like hepatitis which might lead to a faster progression from HIV to AIDS. A recent study from the University of Pennsylvania School of Medicine showed a dramatic increase in the ability of HIV to attack healthy cells when methamphetamine is present in the bloodstream. This indicates that illegal drugs are also aiding in the HIV infection.

Being physically fit through a good work-out three to six times a week can help improve a person’s mood, perspective and overall quality of life. A good amount of moderate exercise can help fight HIV symptoms of nerve pain, loss of appetite and reduce the risks of other chronic diseases like heart disease, diabetes and osteoporosis. Taking the prescribed medication on time is known as adherence. This is vital to help reduce the risk of HIV becoming drug resistant and helps the immune system function for a longer time.

Nowadays, with the help of Internet of Things or IoT, patient’s health can be monitored 24/7. The quality of care provided can be increased many-folds with the help of monitoring devices enabled with current technology [ 26 ]. Concept of E-Health and M-Health is currently trending. E-Health makes use of electronic and communication processes with improved cyber security [ 26 ]. Some of the E-Health devices include GPS tracking, pedometer and electronic health records [ 26 ]. M-Health systems provide doctors with the complete medical history of the patient, so the treatment becomes easier and does not delay in case of emergencies. It makes use of mobile phones and other communication systems to help the patients with information about preventive health care services and collects data in real time as well [ 26 ]. The other important applications include chronic disease management, monitoring of diseases and tracking of epidemic outbreaks [ 26 ].

Genomic Diversity and Clinical Implications

Despite billions of dollars being invested, there is currently no HIV vaccine available that can either prevent the disease or treat those who suffer from it. An AIDS patient harbours 100 million genetically distinct variants of HIV [ 27 ]. This high diversity of HIV-1 is due to high replication rates, errors in reverse transcriptase and recombination events that mainly occur during the viral replication process. Reverse transcriptase enzyme has approximately a rate of 10 –4 nucleotide substitutions per replication cycle. Deletions, insertions and duplications are major contributing factors to the genetic variation of the virus [ 27 ]. Genetic recombination also plays an important role in creating genetic diversity. Template switches between two copies of RNA strands occur regularly during reverse transcription [ 27 ]. This generates a lot of mutations with the help of inter- and intra-molecular jumps. These mutations can either be drug resistant or inhibit the viral replication capacity.

HIV-1 can be classified into four main groups: M, N, O and the recently identified P. The M group is further identified into 4 subtypes (A to J). Studies have shown that there is a worldwide spread of non-B subtype viruses, and with the introduction of antiretroviral drugs, more research has to be conducted regarding the responsiveness of the drug resistance in non-B subtypes [ 27 ]. Different types of HIV-1 resistance are observed in different subtypes at varied levels. For example, subtypes B and G have shown to develop resistance against nelfinavir [ 27 ]. Research is also being done in the role of polymorphisms for development of drug resistance, to assess the genotypes before and after the therapy to be able to establish any association between the two [ 27 ].

Variation of Disease Progression Rate

There are 3 phases of the progression of HIV-1 infection- primary infection, chronic asymptomatic phase of infection and finally, AIDS. In the asymptomatic phase, neither signs nor symptoms of the disease are present, and this phase lasts an average of about 10 years. They can be divided as typical progressors, rapid progressors, slow progressors and long-term progressors. Rapid ones (10–20%) develop AIDS within 5 years of infection [ 28 ]. Slow progressors (5–15%) remain free of AIDS 15 years after infection [ 28 ]. Long-term progressors that constitute 1% show no signs and symptoms [ 28 ]. Factors like host genetic make-up, immune responses, co-infection and viral genetics and adaptation are attribute to this huge variation in disease progression [ 28 ]. But there is no solid evidence as such.

Some individuals known as elite controllers are able to manage the viral replication for longer durations, others are shown to rapidly lose CD4 + T-cells after seroconversion in the absence of cART (combination antiretroviral therapy). Scientists have conducted research studies that has led to the conclusion that rapid progression before administration of cART stops the recovery of CD4 + T-cells once the suppressive response to HIV-1 through cART is achieved. These findings have implications in public health policy making, clinical outcomes and science research. Ideally, cART should be initiated as soon the patient is diagnosed with HIV-1 irrespective of the CD4 + T-cell count. However, in clinical settings where cART is not widely available, these results would support strategies that may help in promoting frequent testing to reduce the proportion of patients initiating cART at low CD4 + T-cell counts. For those testing early, frequent CD4 + T-cell count should be monitored close to the time of HIV diagnoses to establish the rapid progressors phenotype in order to avoid unnecessary CD4 + T-cell count decay among rapid progressors. Finally, interpretation of the immunopathological basis of rapid progression can help improve individual clinical outcomes and limit its impact in the global HIV-1 pandemic.

Development of Drug Resistance as a Major Barrier to Treat HIV

HIV-1 has a high mutation rate. An estimated 10 10 virions per day can be produced in untreated patients that may result in variants called quasispecies. The complexity is also increased due to high recombination rate whenever more than one variant infects the same cell. All these are contributing factors that help in invading the host’s immune system and fostering drug resistance. Salvage therapy is also useful in cases when more than one regimen failed or a single regimen failed for a patient. It can be used to suppress the virus levels below the detection level and should have high genetic barrier to resistance to prevent rebound [ 29 ]. Clinicians need to focus on patient’s adherence as well as access to antiretrovirals (ARVs), drug interactions, tolerability, genotypic and phenotypic resistance testing, cross-resistance, genetic barrier and potency of ARVs [ 29 ].

Overcoming Obstacles and Future Prospects

At present, the reason for not being able to achieve a complete cure with the help of ART, in spite of achievement of undetectable viral load, is due to the presence of dormant virus or HIV latency. In a method call shock and kill, immune stimulants shock the latent virus from hidden reservoirs and then attempt to kill reactivated HIV [ 18 ]. An enzyme has been identified which is called histone deacetylase (HDAC) which is responsible for the sustained latency. Some studies show promise but are yet to be confirmed by clinical trials. Flushing these latent CD4 HIV-infected cells from their reservoirs with these HDAC-inhibitors into the blood circulation makes them susceptible to ART. Vorinostat and panobinostat are two such promising drugs [ 18 ].

Histone deacetylase inhibitors seem to have a broad spectrum of epigenetic activities. Vorinostat (also called Zolinza) is a U.S. Food and Drug Administration approved medicine, which has been used for the treatment of cutaneous T-cell lymphoma (CTCL) [ 18 ]. They help in flushing the virus from the reservoirs into the circulation. The dose is 400 mg. Other drugs on the pipeline are Protein kinase C agonist bryostatin-1 and GS-9620—TLR7 agonist [ 18 ].

Romidepsin (also called Istodax) is another HDAC inhibitor drug, which induces HIV-1 transcription to form plasma HIV-1 RNA that can be easily detected with standard assays [ 18 ]. This gives a possibility of reversing the HIV-1 latency in vivo without hindering T cell mediated immune response [ 18 ]. These findings will help the researchers with future clinical trials aiming to eliminate the HIV-1 reservoirs.

Research for curing HIV is at an infant stage but a promising one. Scientists are working on two broad types of HIV cures—a functional cure and a sterilising one.

The approach of the functional cure is to reduce the virus levels in the body to an undetectable stage, where the patient no longer needs to be on HIV medication or has no risk of progression to AIDS nor transferring the virus to others. Unlike the functional cure, however, a sterilising cure aims to get rid of HIV from the body completely by eliminating cells from latent reservoirs. It has proved to be an extremely challenging task for scientists, who believe it may be unachievable in the majority of them living with HIV. However, some findings by researchers at the University of Pittsburgh could lead to a foundation for an HIV vaccine. Clinical trials are in the works.

Abivax, a French company, is developing a drug that binds to some specific sequence of the viral RNA and inhibits its replication. During clinical trials, it has shown that this may have the potential to become a functional cure. The key is that it can target the reservoir of HIV viruses that hide inactive within our cells. It can target the reservoirs where HIV viruses act as inactive, within the infected cells. The result of phase IIa trial was quite promising. Fifteen patients were given the drug in combination with ART, and it was observed after 28 days of treatment that eight patients showed a 25% to almost 50% reduction of their HIV reservoirs compared to those only taking ART. The company is planning a phase IIb clinical trial to confirm the effects of the drug in the long term.

Research and development in HIV and its cure have come a long way since the disease was discovered in the 1980s. ART was a major milestone that has changed the lives of millions for good, but the next ambitious goal is to find an HIV cure before the year 2020. There are several approaches to an HIV cure ranging from shock and kill therapy, immunotherapy, vaccine development to gene editing using zinc finger nucleases and the CRISPR/Cas9 system, but finding the best possible solution is a challenge. One of the biggest challenges around any HIV treatment is the ability of the virus to rapidly mutate and develop resistance. Many of the new approaches do not provide any valuable insights as to whether the virus has the potential to become resistant. As of now, none of these functional cures have reached late-stage clinical trials, and the aim of finding an HIV cure until 2020 seems far-fetched. However, 2020 will likely be marked as an important milestone as the first late-stage trials will be executed. If successful, it could bring the approval of the first functional HIV cure in ten years.

There are two gene therapies undergoing human trials—one is to destroy the CCR5 receptor of the immune cells of people infected with HIV and the other therapy includes the CRISPR technology which is still under early trials. This mutation does not necessarily protect the person against all types of HIV. It was found that in one of the patients who had received the bone marrow treatment, it was found to have the CXCR4-tropic form. It uses a different type of receptor to enter and infect the cells. It was, however, not known whether this virus was acquired after the treatment or if some patients do contract a small amount of CXCR4-tropic virus that starts to multiply when other types are not present.

HIV research continues on many fronts that could provide the same results and only some of which rely on the CCR5 delta 32 mutation, which should be explored extensively. There are many strategies which are in the early stages of development. Scientific process can be slow but if done correctly, advances can be made to find a scalable, cost-effective cure for everyone.

Acknowledgments

The authors listed in this paper wish to express their appreciation to the RSST trust Bangalore for their continuous support and encouragement.

Authors Contribution

All authors have contributed equally with their valuable comments which made the manuscript to this form.

There was no funding provided for the above research and preparation of the manuscript.

Compliance with Ethical Standards

The authors declare that they have no conflict of interest.

All the authors listed hereby confirmed that in the above research, there were no human participants and/or animals involved in any kind of determination, evaluation or research studies.

There is also final confirmation given by all the listed authors for the submission of manuscript in its actual state. The authors listed above also confirm that the above-mentioned manuscript is in its original state and the manuscript is neither submitted anywhere nor in the submission process in any other journals. In addition, all the authors have solely contributed their original work in the preparation of this manuscript. If the copying or similarity have been found, then in all situations the listed authors are solely responsible.

Significance Statement

This article aims to increase awareness among the society about the current scenario of HIV/AIDS. The scientists are working on 2 types of cures—functional and sterilizing. The path to finding a cure is a promising one as late-phase trials begin in 2020.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Praveen Kumar Gupta, Email: ni.ude.ecvr@atpugkneevarp .

Apoorva Saxena, Email: [email protected] .

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Research & training, advances in hiv/aids research.

For an update on what medical science is doing to fight the global HIV/AIDS pandemic, read a Parade article by NIH Director Francis S. Collins and NIAID Director Anthony S. Fauci, AIDS in 2010: How We're Living with HIV .

Over the past several decades, researchers have learned a lot about the human immunodeficiency virus (HIV) and the disease it causes, acquired immunodeficiency syndrome (AIDS). But still more research is needed to help the millions of people whose health continues to be threatened by the global HIV/AIDS pandemic.

At the National Institutes of Health, the HIV/AIDS research effort is led by the National Institute of Allergy and Infectious Diseases (NIAID). A vast network of NIAID-supported scientists, located on the NIH campus in Bethesda, Maryland, and at research centers around the globe, are exploring new ways to prevent and treat HIV infection, as well as to better understand the virus with the goal of finding a cure. For example, in recent months, NIAID and its partners made progress toward finding a vaccine to prevent HIV infection. Check out other promising areas of NIAID-funded research on HIV/AIDS at http://www.niaid.nih.gov/topics/hivaids/Pages/Default.aspx .

Other NIH institutes, including the Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute on Alcohol Abuse and Alcoholism, also support research to better control and ultimately end the HIV/AIDS pandemic. Some of these researchers have found a simple, cost-effective way to cut HIV transmission from infected mothers to their breastfed infants. Others have developed an index to help measure the role of alcohol consumption in illness and death of people with HIV/AIDS.

Find out more about these discoveries and what they mean for improving the health of people in the United States and all around the globe.

This page last reviewed on August 20, 2015

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HIV Treatment Research and Key Takeaways: Dr. Dieffenbach’s Final Update from CROI 2024

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On Wednesday as the 2024 Conference on Retroviruses and Opportunistic Infections (CROI) was winding down, HIV.gov spoke with NIH’s Dr. Carl Dieffenbach about highlights of long-acting HIV treatment research discussed at the conference. Dr. Dieffenbach is the Director of the Division of AIDS at NIH’s National Institute of Allergy and Infectious Diseases . He spoke with Brian Minalga, MSW, Deputy Director of the NIH-supported  Office of HIV/AIDS Network Coordination Exit Disclaimer . Watch our conversation with Dr. Dieffenbach below:

Research Suggests Possible Expanded Options for Long-Acting HIV Treatment

Dr. Dieffenbach highlighted findings from several clinical trials and a plenary session presented at CROI about current and future options for long-acting antiretroviral treatment (ART) for HIV.

First, he discussed a NIAID-supported randomized clinical trial that found that long-acting ART with cabotegravir and rilpivirine was superior in suppressing HIV replication compared to daily oral ART in adults who had been unable to maintain viral suppression through an oral daily regimen. The LATITUDE study Exit Disclaimer enrolled participants in 31 sites in the United States. Last month, the trial’s Data and Safety Monitoring Board conducted a planned review of interim data and recommended halting randomization and offering all eligible study participants long-acting ART based on its observed superior viral suppression of HIV. At CROI, study leaders reported that the interim analysis of data from 294 participants showed that the chance of experiencing unsuppressed HIV was 7% among people taking long-acting ART compared to 25% among those taking daily oral ART . The likelihood of discontinuing the assigned regimen due to adverse events or experiencing unsuppressed HIV was 10% among people taking long-acting ART compared to 26% among those taking daily ART. These findings were statistically significant. Dr. Dieffenbach observed that these results may support expanding the use of long-acting ART among a broader population. Read the study abstract Exit Disclaimer . Read more in this NIAID news release .

Another ongoing clinical trial reported initial findings on the safety of the same long-acting injectable treatment regimen for adolescents with HIV with a suppressed viral load. The NIH-supported MOCHA study Exit Disclaimer enrolled participants aged 12 to 17 who were virally suppressed in Botswana, South Africa, Thailand, Uganda, and the United States. In what he characterized as very encouraging results, Dr. Aditya Gaur of St. Jude Children's Research Hospital, one of the trial’s co-chairs, reported that after the first six months all participants remained virally suppressed, and the level of the ART in their systems was comparable to what has been shown as efficacious in adult studies of the same drug . He also reported that, while about one-third of the participants reported an injection-site reaction, there were no surprising or unanticipated adverse events. These data support the use of cabotegravir and rilpivirine in virally suppressed adolescents, according to Dr. Gaur and colleagues. Dr. Dieffenbach noted that NIH will continue to support safety and dosing studies to determine the proper doses for adolescents and that these studies could eventually expand access to this long-acting HIV treatment to more people. Read the abstract Exit Disclaimer . Read NIAID’s news release about the study .

In addition, Dr. Dieffenbach mentioned an industry-sponsored Phase 2 trial that presented 24-week results of an oral once-weekly investigational combination of two drugs ( islatravir and lenacapavir ). Researchers reported that the investigational combination maintained a high level of viral suppression among study participants and was well tolerated. The study will continue to gather data and suggests that a weekly oral HIV treatment regimen could someday be possible . Read the abstract Exit Disclaimer .

Finally, Dr. Dieffenbach discussed Wednesday’s plenary session by Dr. Charles Flexner of The Johns Hopkins University School of Medicine, which was titled “The End of Oral? How Long-Acting Formulations Are Changing the Management of Infectious Diseases.” In his big picture, future-focused presentation exploring long-acting drug delivery, Dr. Flexner observed that there is a need for HIV products with less frequent dosing, greater convenience, and greater likelihood of viral suppression, as well as for the prevention and treatment of other diseases, including tuberculosis, malaria, and viral hepatitis. He discussed recent advances in formulation science that are going to help make available better replacements for daily oral drugs for HIV and many other infectious diseases . Dr. Dieffenbach underscored Dr. Flexner’s point that these novel products must be developed with access and equity in mind so that people who need them, especially in resource-limited settings, can use them.

Key Takeaways

Reflecting on key takeaways from the entire conference, both Dr. Dieffenbach and Brian pointed to the importance of partnership between the HIV community and scientists in all aspects of HIV research , a theme also discussed in HIV.gov’s conversation with Dr. LaRon Nelson from the conference. In terms of research highlights, Dr. Dieffenbach pointed to the results reported from the IMPAACT P1115 study in which several children who started HIV treatment within hours of birth later surpassed a year of HIV remission after a treatment pause. ( See HIV.gov’s interview with Dr. Deborah Persaud about this study .) He also noted that the additional data accumulating on the effectiveness of Doxy-PEP is encouraging and will hopefully soon be reflected in clinical guidelines that help to reduce the incidence of syphilis, chlamydia, and gonorrhea in men who have sex with men and transgender women.

Catch Up on More HIV Research Updates

HIV.gov has shared other interviews from CROI 2024 with federal HIV leaders, participating researchers, and community members. You can find all of them on HIV.gov’s social media channels and recapped here on the blog this week and next week.

More than 3,600 HIV and infectious disease researchers from 73 countries gathered in Denver and virtually from March 3-6 this year for CROI, an annual scientific meeting on the latest research that can help accelerate global progress in the response to HIV and other infectious diseases, including STIs and viral hepatitis. Over 1,000 summaries of original research were presented. Visit the conference website Exit Disclaimer for more information. Session webcasts and more information will be published there for public access in 30 days.

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Icymi: research roundup from aids 2024, we should leverage the successes of hiv care to prevent overdose mortality, putting people first: ias closing day.

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New WHO guidance on HIV viral suppression and scientific updates released at IAS 2023

The World Health Organization (WHO) is releasing new scientific and normative guidance on HIV at the 12 th International IAS (the International AIDS Society) Conference on HIV Science .

New WHO guidance and an accompanying Lancet systematic review released today describe the role of HIV viral suppression and undetectable levels of virus in both improving individual health and halting onward HIV transmission. The guidance describes key HIV viral load thresholds and the approaches to measure levels of virus against these thresholds; for example, people living with HIV who achieve an undetectable level of virus by consistent use of antiretroviral therapy, do not transmit HIV to their sexual partner(s) and are at low risk of transmitting HIV vertically to their children. The evidence also indicates that there is negligible, or almost zero, risk of transmitting HIV when a person has a HIV viral load measurement of less than or equal to 1000 copies per mL, also commonly referred to as having a suppressed viral load.

Antiretroviral therapy continues to transform the lives of people living with HIV. People living with HIV who are diagnosed and treated early, and take their medication as prescribed, can expect to have the same health and life expectancy as their HIV-negative counterparts.

“For more than 20 years, countries all over the world have relied on WHO’s evidence-based guidelines to prevent, test for and treat HIV infection,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “The new guidelines we are publishing today will help countries to use powerful tools have the potential to transform the lives of millions of people living with or at risk of HIV.”

At the end of 2022, 29.8 million of the 39 million people living with HIV were taking antiretroviral treatment (which means 76% of all people living with HIV) with almost three-quarters of them (71%) living with suppressed HIV. This means that for those virally suppressed their health is well protected and they are not at risk of transmitting HIV to other people. While this is a very positive progress for adults living with HIV, viral load suppression in children living with HIV is only 46% - a reality that needs urgent attention.

Here is an overview of other key scientific and normative updates being released by WHO at IAS 2023 conference:

HIV and mpox

An analysis of global surveillance data reported to WHO during the multi-country outbreak of mpox, identified that among more than 82 000 mpox cases, around 32 000 cases had information on HIV status. Among those, 52% were living with HIV, most being men who have sex with men (MSM); and more than 80% reported sex as the most probable route of getting infected with mpox.

Among 16 000 people diagnosed with mpox and living with HIV, around one quarter (25%) had advanced HIV disease or immunosuppression – leading to an increased risk of hospitalization and death. People living with HIV who were taking HIV treatment and with good immunity had similar hospitalization and death outcomes as those who were HIV negative.

In the light of these findings, WHO recommends countries integrate mpox detection, prevention, and care with existing and innovative HIV and sexually transmitted infection prevention and control programmes.

To understand how to better prepare for and respond to future increases in mpox transmission, WHO led a rapid electronic survey in May 2023 to assess community experiences of the 2022-2023 mpox outbreak in Europe and the Americas.

More than 24 000 people participated in the survey which focused on men who have sex with men, and trans and gender-diverse people, with 16 875 eligible individuals completing the survey. Almost 51% changed their sexual behaviour (such as reducing the number of sexual partners), and 35% had maintained these changes one year later. Findings from this survey provide valuable insights into the experiences and needs of affected communities and emphasize the importance of increasing access to mpox vaccination and diagnostics globally.

HIV and COVID-19

An updated analysis from WHO global clinical platform for COVID-19 up through May 2023 revealed a persistent high risk of death in people living with HIV hospitalized for COVID-19 across pre-Delta, Delta and Omicron variant waves, with an overall in-hospital mortality rate of 20%-24%. For people without HIV, the risk of death fell during the Omicron variant wave by 53%—55% compared to pre-Delta and Delta variant waves; but for people living with HIV, the percentage decline in mortality during the Omicron wave period compared to the other waves was modest (16%-19%). This difference resulted in a 142 times increased risk of death among people living with HIV when compared with people without HIV during the Omicron wave period. 

Risk factors for in-hospital death that were common across all variant waves of the pandemic were low CD4 count (less than 200 cells per m3), and severe or critical COVID-19 illness at hospital admission.

“Uncontrolled HIV remains a risk factor for poor outcomes and death in the mpox outbreak and COVID-19 pandemic”, said Dr Meg Doherty, Director of WHO’s Global HIV, Hepatitis and Sexually Transmitted Infections Programmes. "We must ensure the integration of HIV considerations in pandemic preparedness and response. Protecting people living with HIV from future pandemics is vital and reinforces the need to ensure access to HIV testing and treatment and preventive vaccines for mpox and COVID-19 to save lives; community-led responses that work for HIV will also be beneficial for addressing future pandemics."

Optimizing HIV testing services through expanded testing options and simplified service delivery

With new recommendations on HIV testing , WHO is calling on countries to expand use of HIV self-testing and promote testing through sexual and social networks to increase testing coverage and strengthen uptake of HIV prevention and treatment services in high-burden settings and in regions with the greatest gaps in testing coverage.

The recommendation comes at a pivotal time, where self-care and self-testing are increasingly being recognized as ways to increase access, efficiency, effectiveness and acceptability of health care across many different disease areas, including HIV.

Primary health care and HIV

A new policy framework on primary health care (PHC) and HIV will help decision-makers optimize work and collaboration underway to advance primary health care and disease-specific responses, including HIV. In the second year of implementation, the Global Health Sector Strategies on HIV, viral hepatitis and sexually transmitted infections for 2022-2030 actively advocate for synergies within the framework of universal health coverage and primary health care.

“Ending AIDS is impossible without optimizing opportunities across and within health systems, including with communities and in the context of primary health care”, said Dr Jérôme Salomon, WHO Assistant Director-General, Universal Health Coverage, Communicable and Noncommunicable Diseases.

This latest research and guidance are being presented at a time when progress towards ending the global AIDS epidemic has lagged, after the COVID-19 pandemic; but the response is rapidly catching up, with some countries now charting a path to end AIDS , including Australia, Botswana, Eswatini, Rwanda, United Republic of Tanzania, and Zimbabwe and 16 other countries that are close to reaching the 95-95-95 global targets, which aim for 95% of people living with HIV knowing their status, 95% of those diagnosed receiving ART and 95% of those on treatment having suppressed viral loads.

Note to the editor:

12th IAS Conference on HIV Science

The IAS 2023, the 12th IAS Conference on HIV Science will be held in Brisbane from 23 to 26 July 2023. This biennial conference presents the critical advances in basic, clinical and operational HIV research that move science into policy and practice.

For more detailed information on WHO at the conference, visit: https://who.int/news-room/events/detail/2023/07/23/default-calendar/who-at-ias-conference-2023

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There’s New Hope for an HIV Vaccine

Since it was first identified in 1983, HIV has infected more than 85 million people and caused some 40 million deaths worldwide.

While medication known as pre-exposure prophylaxis , or PrEP, can significantly reduce the risk of getting HIV, it has to be taken every day to be effective. A vaccine to provide lasting protection has eluded researchers for decades. Now, there may finally be a viable strategy for making one.

An experimental vaccine developed at Duke University triggered an elusive type of broadly neutralizing antibody in a small group of people enrolled in a 2019 clinical trial. The findings were published today in the scientific journal Cell .

“This is one of the most pivotal studies in the HIV vaccine field to date,” says Glenda Gray, an HIV expert and the president and CEO of the South African Medical Research Council, who was not involved in the study.

A few years ago, a team from Scripps Research and the International AIDS Vaccine Initiative (IAVI) showed that it was possible to stimulate the precursor cells needed to make these rare antibodies in people. The Duke study goes a step further to generate these antibodies, albeit at low levels.

“This is a scientific feat and gives the field great hope that one can construct an HIV vaccine regimen that directs the immune response along a path that is required for protection,” Gray says.

Vaccines work by training the immune system to recognize a virus or other pathogen. They introduce something that looks like the virus—a piece of it, for example, or a weakened version of it—and by doing so, spur the body’s B cells into producing protective antibodies against it. Those antibodies stick around so that when a person later encounters the real virus, the immune system remembers and is poised to attack.

While researchers were able to produce Covid-19 vaccines in a matter of months, creating a vaccine against HIV has proven much more challenging. The problem is the unique nature of the virus. HIV mutates rapidly, meaning it can quickly outmaneuver immune defenses. It also integrates into the human genome within a few days of exposure, hiding out from the immune system.

“Parts of the virus look like our own cells, and we don’t like to make antibodies against our own selves,” says Barton Haynes, director of the Duke Human Vaccine Institute and one of the authors on the paper.

The particular antibodies that researchers are interested in are known as broadly neutralizing antibodies, which can recognize and block different versions of the virus. Because of HIV’s shape-shifting nature, there are two main types of HIV and each has several strains. An effective vaccine will need to target many of them.

Some HIV-infected individuals generate broadly neutralizing antibodies, although it often takes years of living with HIV to do so, Haynes says. Even then, people don’t make enough of them to fight off the virus. These special antibodies are made by unusual B cells that are loaded with mutations they’ve acquired over time in reaction to the virus changing inside the body. “These are weird antibodies,” Haynes says. “The body doesn’t make them easily.”

Haynes and his colleagues aimed to speed up that process in healthy, HIV-negative people. Their vaccine uses synthetic molecules that mimic a part of HIV’s outer coat, or envelope, called the membrane proximal external region. This area remains stable even as the virus mutates. Antibodies against this region can block many circulating strains of HIV.

The trial enrolled 20 healthy participants who were HIV-negative. Of those, 15 people received two of four planned doses of the investigational vaccine, and five received three doses. The trial was halted when one participant experienced an allergic reaction that was not life-threatening. The team found that the reaction was likely due to an additive in the vaccine, which they plan to remove in future testing.

Still, they found that two doses of the vaccine were enough to induce low levels of broadly neutralizing antibodies within a few weeks. Notably, B cells seemed to remain in a state of development to allow them to continue acquiring mutations, so they could evolve along with the virus. Researchers tested the antibodies on HIV samples in the lab and found that they were able to neutralize between 15 and 35 percent of them.

Jeffrey Laurence, a scientific consultant at the Foundation for AIDS Research (amfAR) and a professor of medicine at Weill Cornell Medical College, says the findings represent a step forward, but that challenges remain. “It outlines a path for vaccine development, but there’s a lot of work that needs to be done,” he says.

For one, he says, a vaccine would need to generate antibody levels that are significantly higher and able to neutralize with greater efficacy. He also says a one-dose vaccine would be ideal. “If you’re ever going to have a vaccine that’s helpful to the world, you’re going to need one dose,” he says.

Targeting more regions of the virus envelope could produce a more robust response. Haynes says the next step is designing a vaccine with at least three components, all aimed at distinct regions of the virus. The goal is to guide the B cells to become much stronger neutralizers, Haynes says. “We’re going to move forward and build on what we have learned.”

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After decades of failures, researchers have renewed hopes for an effective HIV vaccine

The world needs an HIV vaccine if it ever hopes to beat a virus that still infects over 1 million people a year and contributes to hundreds of thousands of deaths.

Despite 20 years of failures in major HIV vaccine trials — four this decade alone — researchers say recent scientific advances have likely, hopefully, put them on the right track to develop a highly effective vaccine against the insidious virus.

But probably not until the 2030s. 

“An effective vaccine is really the only way to provide long-term immunity against HIV, and that’s what we need,” Dr. Julie McElrath, the director of the vaccine and infectious disease division at the Fred Hutchinson Cancer Center in Seattle, said Monday at the Conference on Retroviruses and Opportunistic Infections in Denver.

All current HIV vaccine action is in the laboratory, animal studies or very early human trials.

Researchers at the retrovirus conference presented favorable results from two HIV vaccine studies. One found that a modification to the simian version of HIV spurred production of what are known as broadly neutralizing antibodies against the virus in monkeys. Another showed promise in the effort to coax the immune system’s B cells to make the powerful antibodies in humans. 

“These trials illustrate as a proof of concept that we can train the immune system. But we need to further optimize it and test it in clinical trials,” Karlijn van der Straten, a Ph.D. student at the Academic Medical Center at Amsterdam University, who presented the human study, said at a news conference Monday.

Still, the scrappy scientists in this field face a towering challenge. HIV is perhaps the most complex pathogen ever known. 

“The whole field has learned from the past,” said William Schief, who leads Moderna’s HIV vaccine efforts. “We’ve learned strategies that don’t work.”

The cost has already been immense. Nearly $17 billion was spent worldwide on HIV -vaccine research from 2000 to 2021. Nearly $1 billion more is spent annually, according to the Joint United Nations Program on HIV/AIDS and the nonprofit HIV group AVAC.

“Maintaining the funding for HIV vaccines right now is really important,” said Dr. Nina Russell, who directs HIV research at the Bill & Melinda Gates Foundation. She pointed to the field’s own “progress and the excitement” and to how “HIV vaccine science and scientists continue to drive innovation and science that benefits other infectious diseases and global health in general.” 

Case in point: Covid. Thanks to HIV research, the mRNA vaccine technology was already available in 2020 to speed a coronavirus vaccine to market.

Why the HIV vaccine efficacy trials failed

In strong contrast to Covid, the HIV vaccine endeavor has spanned four decades. Only one of the nine HIV vaccine trials have shown efficacy: a trial conducted in Thailand and published in 2009 that reported a modest 31% reduction in HIV risk.

HIV vaccine researchers subsequently spent years seeking to retool and improve that vaccine strategy, leading to a series of trials that launched in the late 2010s — only to fail.

Researchers have concluded those latest trials were doomed because, aside from prompting an anti-HIV response based in immune cells, they only drove the immune system to produce what are known as non-neutralizing antibodies. Those weapons just weren’t strong enough for such a fearsome foe.

Preventing HIV through vaccination remains a daunting challenge because the immune system doesn’t naturally mount an effective defense against the virus, as it does with so many other vaccine-preventable infections, including Covid. An HIV vaccine must coax from the body a supercharged immune response with no natural equivalent.

That path to victory is based on a crucial caveat: A small proportion of people with HIV do produce what are known as broadly neutralizing antibodies against the virus. They attack HIV in multiple ways and can neutralize a swath of variants of the virus.

Those antibodies don’t do much apparent good for people who develop them naturally, because they typically don’t arise until years into infection. HIV establishes a permanent reservoir in the body within about a week after infection, one that their immune response can’t eliminate. So HIV-positive people with such antibodies still require antiretroviral treatment to remain healthy.

Researchers believe that broadly neutralizing antibodies could prevent HIV from ever seeding an infection, provided the defense was ready in advance of exposure. A pair of major efficacy trials, published in 2021 , demonstrated that infusions of cloned versions of one such antibody did, indeed, protect people who were exposed to certain HIV strains that are susceptible to that antibody. 

However, globally, those particular strains of the virus comprise only a small subset of all circulating HIV. That means researchers can’t simply prompt a vaccine to produce that one antibody and expect it to be effective. Importantly, from this study they got a sense of what antibody level would be required to prevent infection. 

It’s a high benchmark, but at least investigators now have a clearer sense of the challenge before them. 

Also frustrating the HIV vaccine quest is that the virus mutates like mad. Whatever spot on the surface of the virus that antibodies target might be prone to change through mutation, thus allowing the virus to evade their attack. Consequently, researchers search for targets on the virus’ surface that aren’t highly subject to mutation.

Experts also believe warding off the mutation threat will require targeting multiple sites on the virus. So researchers are seeking to develop a portfolio of immune system prompts that would spur production of an array of broadly neutralizing antibodies.

Prompting the development of such antibodies requires a complex, step-by step process of coaxing the infection-fighting B cells, getting them to multiply and then guiding their maturation into potent broadly neutralizing antibody-producing factories.

HIV vaccine development ‘in a better place’

Dr. Carl Dieffenbach, the head of the AIDS division at the National Institute of Allergy and Infectious Diseases, said numerous recent technological advances — including mRNA, better animal models of HIV infection and high-tech imaging technology — have improved researchers’ precision in designing, and speed in producing, new proteins to spur anti-HIV immune responses.

Global collaboration among major players is also flourishing, researchers said. There are several early-stage human clinical trials of HIV-vaccine components underway.

Three mRNA- based early human trials of such components have been launched since 2022. Among them, they have been led or otherwise funded by the global vaccine research nonprofit group IAVI, Fred Hutch, Moderna, Scripps Research, the Gates Foundation, the National Institutes of Health, the U.S. Agency for International Development, and university teams. More such trials are in the works.

On Friday, Science magazine reported concerning recent findings that among the three mRNA trials, a substantial proportion of participants — 7% to 18%, IAVI said in a statement — experienced skin-related symptoms following injections, including hives, itching and welts.

IAVI said in its statement that it and partners are investigating the HIV trials’ skin-related outcomes, most of which were “mild or moderate and managed with simple allergy medications.” 

Researchers have shown success in one of those mRNA trials in executing a particular step in the B-cell cultivation process.

That vaccine component also generated “helper” CD4 cells primed to combat HIV. The immune cells are expected to operate like an orchestra conductor for the immune system, coordinating a response by sending instructions to B cells and scaling up other facets of an assault on HIV.

A complementary strategy under investigation seeks to promote the development of “killer” CD8 cells that might be primed to kill off any immune cells that the antibodies failed to save from infection.

Crucially, investigators believe they are now much better able to discern top vaccine component candidates from the duds. They plan to spend the coming years developing such components so that when they do assemble the most promising among them into a multi-pronged vaccine, they can be much more confident of ultimate success in a trial.

“An HIV vaccine could end HIV,” McElrath said at the Denver conference. “So I say, ‘Let’s just get on with it.”

Dr. Mark Feinberg, president and CEO of IAVI, suggested that the first trial to test effectiveness of the vaccine might not launch until 2030 or later.

Even so, he was bullish.

“The field of HIV vaccine development is in a better place now than it’s ever been,” he said.

Benjamin Ryan is independent journalist specializing in science and LGBTQ coverage. He contributes to NBC News, The New York Times, The Guardian and Thomson Reuters Foundation and has also written for The Washington Post, The Nation, The Atlantic and New York.

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Office of AIDS Research

• HIV Policy and Research
• Research Priorities
• NIH Strategic Plan for HIV and HIV-Related Research
• NIH HIV Research Budget
• NIH HIV Research Priority Areas
• Reduce the Incidence of HIV
• Develop Next-Generation HIV Therapies

Research Toward HIV Cure

• Address HIV-Associated Comorbidities, Coinfections, & Complications
• Cross-Cutting Areas

Viral latency and sanctuaries

Latent HIV reservoirs—small amounts of HIV that persist in people taking ART—present a significant challenge to finding a cure for HIV. Latent reservoirs remain in people with HIV when HIV becomes part of the body’s DNA in infected cells. Additionally, reservoirs of HIV can be found in certain “sanctuary” sites in the body that allow the virus to hide and be protected from both the immune system and ART. To cure HIV, the NIH supports studies to develop novel approaches and treatments that target these HIV reservoirs.

Sustained viral remission and viral eradication

Current science suggests that the path to an HIV cure involves first achieving sustained viral remission without ART. This is called sustained ART-free viral remission or a functional cure. For sustained ART-free viral remission, infectious virus must remain undetectable by sensitive testing methods for a long time without treatment. One research aim will be to prolong the time between treatments to be measured eventually not in weeks, but in months or even years. The NIH supports research into treatments leading to sustained ART-free viral remission . New cure-inducing treatments must be as safe, effective, and available for widespread use as are current-day ART regimens.

Viral eradication—eliminating the virus entirely—is the more challenging, longer-term goal.

Research Strategies

The NIH supports research to better understand how the HIV reservoir forms, persists, and reactivates, as well as investigations to develop new cure treatment strategies targeting HIV reservoirs.

A range of biomarkers and techniques, including single-cell and imaging technologies, are being studied to determine how to identify and describe the HIV reservoir. These techniques also are being used to better understand mechanisms of viral reactivation from latently infected cells.

Experimental treatments in development include therapeutic vaccines, genetically engineered immune cells that are resistant to HIV infection, drugs that reactivate latent HIV to make the virus visible to the immune system, cure-inducing immunotherapies, and interventions to permanently silence HIV in infected cells.

The search for an HIV cure involves important behavioral and social processes that complement the domains of biomedicine.  BSSR in HIV cure research is focused on important aspects such as: counseling and support interventions to address the psychosocial needs and concerns of study participants related to analytical treatment interruptions (ATIs); risk reduction in the course of ATI study participation; motivation, acceptability, and decision‐making processes of potential study participants; how cure affects the identity and social position of people with HIV; and the scalability of a proven cure strategy in the context of further advances in HIV prevention and treatment.

The NIH is leveraging resources toward an HIV cure through several public-private partnerships. NIH small business awards enable companies to help foster a diverse pipeline of experimental treatments in development. The combined support of government, industry, and nongovernmental foundations is fostering the expansion of a talented scientific workforce dedicated to advancing HIV cure research.

OAR scientist Dr. Paul Sato coordinates Research Toward an HIV Cure .

This page last reviewed on September 8, 2022

Childhood HIV Vaccination Strategy Shows Promise in Study

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Weill Cornell Medicine researchers have developed an experimental vaccine to protect against  human immunodeficiency virus (HIV) infection based on " spike" proteins (shown in purple) on the surface of the virus. Credit: Shutterstock

Research at Weill Cornell Medicine suggests that childhood immunization against HIV could one day provide protection before risk of contracting this potentially fatal infection dramatically increases in adolescence.   

The study , published Aug. 30 in Science Immunology, demonstrated that a series of six vaccinations containing a modified protein from the surface of HIV particles stimulated initial steps of a potent immune response in young non-human primates. This difficult-to-achieve response represents an important step toward providing full and potentially life-long protection against the virus, the researchers say.

Immunizing young children, rather than adults, makes sense because risk factors for HIV infection rise steeply when adolescents become sexually active, according to senior author Dr. Sallie Permar , the Nancy C. Paduano Professor in Pediatrics and chair of the Department of Pediatrics at Weill Cornell Medicine. 

What’s more, evidence suggests that the immune systems of infants and children generally mount more effective responses to the virus than those of adults, said Dr. Permar. “One of the advancements we’ve made is to demonstrate that an HIV vaccine could be delivered on a schedule similar to routine vaccines already given to babies and children.”

Prepping the Immune System Early

HIV predominantly infects immune cells called CD4 T cells, leaving individuals vulnerable to opportunistic diseases. Without lifelong treatment, infection is fatal. In 2022, an estimated 140,000 adolescents between 10 and 19 years old worldwide became infected with the virus—a group that is overrepresented in the number of new infections.

Dr. Sallie Permar

Vaccine researchers are seeking ways to stimulate the immune system to make “broadly neutralizing antibodies” against the virus before a person is exposed to it. These antibodies attack a crucial part of the HIV virus—the protein on its surface that binds to CD4 T cells. In doing so, broadly neutralizing antibodies prevent many strains of HIV from entering the cell and infecting it.

In this study, the researchers started with an experimental vaccine developed previously from spike proteins on the envelope of HIV particles. Study authors Dr. John Moore , a professor of microbiology and immunology, and Dr. Rogier Sanders , an adjunct associate professor of research in microbiology and immunology at Weill Cornell Medicine and a professor at Amsterdam UMC , sought to improve this vaccine by altering the viral protein. They designed these changes to stimulate a specific set of antibody-producing B cells that protect CD4 T cells. 

“An effective HIV vaccine needs to engage the right set of B cells in order to generate a broadly protective response,” said first author Dr. Ashley Nelson , an assistant professor of immunology research in pediatrics at Weill Cornell Medicine. “We discovered that introducing certain mutations into the envelope protein could accomplish that in the setting of a naïve immune system.”

Activating the Right B Cells for Protection

The researchers administered the modified vaccine to five young primates in three priming doses, starting less than a week after birth. They followed up with three doses of the vaccine matching the original HIV envelope protein, with the last dose given when the animals reached 78 weeks old, roughly equivalent to four or five years old for a human. As a control, five animals received all six doses of the original envelope protein vaccine.

Dr. Ashley Nelson

“While exposure to the modified protein got the immune response started off in the right direction, booster shots containing the original version of the viral protein were necessary to reach full potential,” Dr. Nelson said.

Three of the five animals who received the modified version of the priming vaccine developed antibodies that appeared to be precursors to the sought-after broadly neutralizing response. Tests suggested these antibodies attacked the site the virus uses to invade CD4 T cells. However, they were not yet fully effective against the same breadth of HIV strains as mature broadly neutralizing antibodies. One of the three animals also showed signs of developing the mature, broadly neutralizing response.  

The next step is figuring out how to reliably elicit a full-on broadly neutralizing response, Dr. Nelson said. “We still need to identify the right combination of viral proteins to get us further down that path, starting from the earliest stages in life when multi-dose vaccines are commonly given.”

Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, please see the profile for  Dr. Sallie Permar .

This work was supported in part by National Institutes of Health (NIH) grant P01 AI117915, Office of Research Infrastructure Program/OD grant P51 OD011107 and by the National Institute of Allergy and Infectious Diseases of the NIH grant P01 AI110657.

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Single-shot HIV treatment suppresses virus 10,000-fold for months, animal study finds

Engineered virus-like particles can outcompete HIV in the body, potentially offering long-term viral suppression after a single dose, a monkey study suggests.

Researchers have developed an experimental HIV treatment that sustains itself in the body, with the goal of controlling virus levels for the long term after a single dose.

So far, the new treatment has been tested in monkeys, not people. But in the monkeys, it dramatically suppressed HIV for at least seven months. If the drug is approved for people someday, its protection might last years, said Adrian Wildfire , a virologist and drug development scientist who was not involved in the research.

"I suspect you'll see some decline in function [of the treatment] after five to seven years," Wildfire told Live Science. That represents a big jump from current treatment options.

About 40 million people worldwide are living with HIV, but only about three-quarters of them are currently receiving antiretroviral therapy, the standard treatment. A smaller percentage are virally suppressed , meaning the amount of HIV in their body has declined to extremely low levels.

Related: We could end the AIDS epidemic in less than a decade. Here's how.

Some people face difficulties obtaining an HIV diagnosis and therapy prescription; others may struggle to afford medication, tolerate its side effects, or remember to take the daily pills many treatment regimens require to keep the virus at bay. Some existing long-acting shots last weeks or months, but people typically need to reach suppression with pills before qualifying for the shots.

Complicating the challenge, the virus also evolves very quickly , meaning it can become resistant to treatments, especially if doses are missed . Without treatment, HIV rapidly destroys a key class of immune cell in the body, leaving the person vulnerable to cancers and infectious diseases. At this stage, the infection has progressed to acquired immunodeficiency syndrome (AIDS).

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To overcome some of the issues with existing antiretrovirals, a group of researchers developed a new type of treatment: an engineered form of the virus that can outcompete HIV in the body.

In a study published Aug. 9 in the journal Science , the researchers used genetic engineering to create a version of HIV called a therapeutic interfering particle (TIP). This virus-like particle is designed not to harm its host, but it still replicates quickly. The idea is that, when injected into a person with HIV, the harmless TIP takes over, occupying and protecting cells that the virus would otherwise destroy.

To test that theory, the researchers developed a version of their TIP that resembled simian immunodeficiency virus (SIV), an HIV-like pathogen that infects monkeys. They injected it into six rhesus macaques ( Macaca mulatta ). After 24 hours, they infected the macaques with an aggressive virus with features of both SIV and HIV and tracked levels of infection for about seven months.

They found that the macaques that received TIPs had 10,000 times lower levels of virus than four infected monkeys that hadn't received the shot. The TIP-injected monkeys also had stronger immune responses and no evidence of inflammation . The untreated monkeys had quickly developed severe illnesses.

Related: People on HIV meds have 'almost zero' chance of spreading virus via sex once levels are low

As designed, the TIPs continued to replicate in the macaques' bodies throughout the entire study period, hinting that long-lasting treatment may be possible.

"These primate studies show the promise of a single-dose TIP intervention and are a strong indicator of efficacy in human trials," senior study author Leor Weinberger , a professor of pharmaceutical chemistry, biochemistry and biophysics at the University of California, San Francisco, said in a statement .

The researchers also applied their TIPs to lab mice with human immune cells and to blood cells from people living with HIV. In both cases, the TIPs outcompeted HIV and suppressed the infection.

"You're reducing viral replication a lot, which could allow people to live with fewer symptoms because far fewer of their T cells are being destroyed," Wildfire told Live Science. But he doesn't think the treatment will last indefinitely.

Because of their similarity to unmodified viruses, TIPs stimulate various immune cells in the body that can eventually become exhausted by this. This opens the door for more TIPs and HIV to enter cells — but since HIV continually evolves, this exhaustion could theoretically allow HIV to gain a foothold over TIPs.

— HIV prevention drug found 100% effective in clinical trial

— New trial hints at a possible HIV cure approach: Wake up latent virus hiding in the body, then kill it

— Could CRISPR cure HIV someday?

"So what's the outlook on this? Relatively positive in the short term, but I think more work is needed in the long run," Wildfire said.

The researchers have not yet tested whether this new treatment could replace antiretroviral drugs for people who are already living with well-controlled HIV. Their next step is to test this idea in macaques, after which they hope to embark on human clinical trials. The end goal is to offer new options for HIV treatment so people won't have to take medications continually for the rest of their lives.

Ever wonder why some people build muscle more easily than others or why freckles come out in the sun ? Send us your questions about how the human body works to [email protected] with the subject line "Health Desk Q," and you may see your question answered on the website!

Michael Schubert is a veteran science and medicine communicator. He writes across all areas of the life sciences and medicine but specializes in the study of the very small — from the genes that make our bodies work to the chemicals that could support life on other planets. Mick holds graduate degrees in medical biochemistry and molecular biology. When he's not writing or editing, he is co-director of the Digital Communications Fellowship in Pathology; a professor of professional practice in academic writing at ThinkSpace Education; an inclusion and accessibility consultant; and (most importantly) dog-walker and ball-thrower extraordinaire.

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The FDA has approved a new drug in the fight against AIDS

Jason Beaubien

The Food and Drug Administration has approved the first injectable medication for HIV prevention. Health advocates say it could be a game changer in protecting people against AIDS

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NPR transcripts are created on a rush deadline by an NPR contractor. This text may not be in its final form and may be updated or revised in the future. Accuracy and availability may vary. The authoritative record of NPR’s programming is the audio record.

Future Directions for HIV Treatment Research

A major goal of NIAID-supported research on HIV treatment today is to develop long-acting therapies that—unlike current antiretrovirals, which require daily dosing—could be taken only once a week, once a month, or even less often. Such long-acting therapies might be easier for some people to stick to than daily pills, and might also be less toxic and more cost effective. The three types of agents under study are long-acting drugs, broadly neutralizing antibodies, and therapeutic vaccines.

Long-Acting Drugs

NIAID-supported scientists aim to develop a new array of drugs for HIV treatment that include longer-acting pills as well as alternative formulations such as injections, patches, and implants. The complexity of developing such products has led NIAID to create a consortium of experts who can facilitate relationships among the many types of researchers needed to translate an idea for a long-acting HIV drug into a workable solution. Called LEAP, for Long-Acting/Extended Release Antiretroviral Resource Program, the consortium includes scientists and clinicians from academia, industry, and government, as well as patient advocates. Read more about LEAP.

NIAID also will investigate the effectiveness of two investigational long-acting HIV drugs, rilpivirine LA and cabotegravir LA, in people for whom adhering to conventional antiretroviral therapy has been a challenge. Another study is planned to test whether the combination of monthly injections of cabotegravir LA and monthly infusions of an NIAID-discovered broadly neutralizing antibody called VRC01LS can keep HIV suppressed in people whose infection was previously controlled by antiretroviral therapy. 

Broadly Neutralizing Antibodies

Scientists at the NIAID Vaccine Research Center (VRC) and NIAID-supported scientists at other institutions are developing and testing multiple antibodies for the treatment of HIV. Antibodies are good candidates for treatment because they have few side effects and can be modified to ensure they last a long time in the body, suggesting that dosing could be every other month or even less often. Importantly, the antibodies under investigation can powerfully stop a wide range of HIV strains from infecting human cells in the laboratory and thus are known as broadly neutralizing antibodies, or bNAbs.

In the context of treatment, bNAbs can potentially thwart HIV in three ways:

• By binding directly to the virus, preventing it from entering a cell and accelerating its elimination.
• By binding to an HIV-infected cell, recruiting immune-system components that facilitate cell killing.
• By binding to a key fragment of HIV, forming a complex that may lead to the stimulation of immune cells in a manner similar to a vaccine, thereby preparing the immune system for future encounters with the virus.

Clinical studies have established that giving infusions of certain bNAbs to people living with HIV can suppress the virus, albeit to a limited degree. Further studies have shown that treating people living with HIV with just one bNAb fosters the emergence of HIV strains that are resistant to the antibody. Thus, just as antiretroviral therapy requires a combination of drugs to effectively suppress HIV, it appears that antibody-based therapy will require a combination of either multiple bNAbs or bNAbs and long-acting drugs to suppress the virus. Studies in monkeys infected with a simian version of HIV have already demonstrated that combinations of complementary bNAbs powerfully suppress the virus for an extended period. NIAID is now funding and conducting clinical trials of this strategy for treating HIV in people.

In addition, scientists are engineering changes to known bNAbs to optimize them for HIV treatment and prevention applications. These changes are designed to increase the number of HIV strains an antibody can block, how long the antibody lasts in the body, how powerfully the antibody attaches to the virus, and how efficiently the antibody triggers the immune system to attack both the virus and HIV-infected cells.

Therapeutic HIV Vaccines

Perhaps the ideal treatment for HIV infection would be a therapeutic vaccine. Unlike a vaccine designed to prevent HIV infection, a therapeutic vaccine would be given to people already infected with the virus. Such a vaccine would stimulate the immune system to be ready to control any future emergence of HIV and thereby end the need for further therapy, perhaps save periodic booster shots. Such an approach could lead to sustained viral remission , meaning treatment or vaccination that would result in prolonged undetectable levels of HIV without regular antiretroviral therapy.

The presence of rare people living with HIV who can control the virus naturally either from the time of infection or after halting antiretroviral therapy is evidence that a therapeutic vaccine could theoretically alter the immune system to achieve long-term control of HIV. Nevertheless, attempts to create effective therapeutic HIV vaccines have so far been unsuccessful. To help improve results, NIAID is working to advance the underlying science—in particular, to improve understanding of immune responses that sustainably suppress HIV and to improve the potency of those responses.

Three of the NIAID-funded Martin Delaney Collaboratories are pursuing strategies that involve therapeutic vaccines to achieve long-term control of HIV or reduction of the reservoir of all virus-carrying cells. Read more about the  Martin Delaney Collaboratories .  

Future Directions for Developing Daily HIV Drugs

At the same time, NIAID continues to support research to develop new drugs with unique mechanisms of action for daily antiretroviral therapy. Such drugs likely would be effective against HIV strains with resistance to other drug types.

For example, basic NIAID-supported research contributed to development of the experimental drug islatravir (also known as EFdA or MK-8591), which belongs to a class of drugs known as nucleoside reverse transcriptase translocation inhibitors, or NRTTIs. NIAID research also contributed to the development of maturation inhibitors, investigational drugs that target the same stage of the HIV lifecycle as protease inhibitors but act by a different mechanism.

Researchers also are attempting to target other parts of the HIV lifecycle. For example, the experimental inhibitor fostemsavir blocks HIV from infecting immune cells by attaching to the gp120 protein on the virus’ surface. Another example is development of capsid assembly inhibitors, which halt construction of the viral capsid, the protein shell that encloses HIV’s genetic material.

For more information on investigational antiretroviral treatments, see the AIDS info Drug Database.

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Home / Innovation & Research / The innovative research behind HIV/AIDS treatment

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It’s been 40 years since the release of the first scientific report describing acquired immune deficiency syndrome (AIDS). Thanks to innovative research, scientists learned how the HIV virus that causes AIDS replicates and how the immune system responds to the virus. Today, many people with HIV take just one pill a day to suppress the virus, and treatment is continuing to evolve.

In this video, Dr. Stacey Rizza , Mayo Clinic infectious disease physician and HIV researcher, explains how dedicated innovative science contributed to where we are today and what scientists are working on for the future.

What did the early research find?

Because of truly dedicated innovative science, within a few years, the scientific community figured out that AIDS was due to HIV. It then took a few years to figure out how to test for that virus. Several years later, the scientific community was able to quantitate how much virus was in a person’s blood. During all this time, truly innovative research into how the virus replicates and how the immune system responds to the virus allowed bio pharmacy companies to develop what we call anti-retroviral drugs or medications to slow down the viral replication. How has medication to treat HIV evolved?

The first drug approved for HIV was in 1987, which was AZT (now known as zidovudine). At that time, it was the fastest drug ever approved by the FDA (Food and Drug Administration) and started the fast-track mechanism through the FDA.

Then several other drugs within that same class were approved in the early 1990s. In late 1995, very early 1996, the first HIV protease inhibitors were approved. At that point, it was possible to combine three different medications from two different classes and completely suppress the HIV replication.

In the last 20 years, we’ve gone from people taking multiple medicines with lots of side effects to many of my patients with HIV now take a single pill a day. That’s a combination of medicines coformulated into one pill a day that’s extremely well-tolerated and completely suppresses their virus. We know it does not eliminate the virus. If they were to stop taking that medicine, the virus would come back. But we now have a handful of people in the world who have been what we called functionally cured of HIV, meaning they’ve gone through some research protocols that eliminated the reservoir of HIV in their body.

The new drugs are so effective in people who have fully suppressed virus that many only need to use two medications to maintain HIV treatment and control. New research is investigating ways to deliver the medications differently, such as a shot that lasts several months, or maybe someday even implantable medication delivery mechanisms so that people don’t have to take the pill every day. It is very exciting that HIV therapy is moving that direction.

Why isn’t there a cure for HIV?

The reason why it is so difficult to cure HIV is that once HIV infects a person’s body, it integrates into the host genome of several cell types. Those cells then hide in any of the lymphoid tissue, such as the lymph nodes, the liver and the spleen. And they lay there as what we call “latent” or “hiding”, as long as the person is on HIV therapy. Anytime a virus does leave a cell, it gets taken care of by HIV therapy. But if the infected individual stops the HIV therapy, that latent virus will come back. To cure HIV, you have to eliminate those hiding viruses in the cells or that latent viral reservoir, which is the term. There are many ways you can approach eliminating the reservoir.

Where is the research now?

One of the more popular ways that have been investigated is something called — and there are many different terms for it — “prime, shock, and kill” or “kick, and kill”, which is essentially giving medications that first wake the virus up from latency and then find ways to make the cells that have the virus susceptible to dying. When the virus is awake, and the cell is susceptible to dying, it kills itself but does not kill any other cells in the body.

Essentially, it specifically targets the HIV-infected cells and eliminates them without hurting anything else. This new science is exciting. It’s getting closer and closer to understanding how to do this effectively. And if you can do that with oral medications rather than fancy therapies like gene therapy or bone marrow transplant, it’s scalable to large parts of the world, and you can touch millions of people that way. That’s where the area of research is on how to make those hiding cells wake up, how to make them sensitive to die, and how to target just the HIV-infected cell.

Will we see a vaccine for HIV?

HIV has been a very hard vaccine to develop. In the world of viruses, vaccines fall into one of three buckets. They fall into the bucket where they respond to antibodies induced by the vaccine, and the vaccines are outstanding. Such viruses include polio, mumps, and lucky for us, SARS-CoV-2. Then we have the second category, like the influenza vaccine, which is about 60% effective. It certainly saves lives and makes a difference, but it’s not perfect. And then we have the third bucket, which quite frankly is the vast majority of viruses that infect humans. And HIV is in that category, where simply forming an antibody to the virus is not adequate to prevent infection. You have to do very sophisticated engineering to induce T cell effects, as well as innate effects and antibody effects. Even then, sometimes it’s very hard to decide what is the part of the virus to target. After decades, and billions of dollars of research, we’re still not there for HIV. There have been many approaches of how to do this science. Many different scientific delivery mechanisms, many different areas of the viruses targeted, many different parts of the immune system targeted, and so far, none of them have been effective at preventing HIV infection.

What needs to happen next?

We still need to slow down the number of people getting infected through good public health measures and good education to stop the HIV epidemic. We still need to get more people who are infected on therapy.

We know we can do it with public health measures. But we also need to find out more about how we eliminate that reservoir and get people cured of the virus in a simple and effective way so that we can cure more people. And the last major hurdle we have is to develop an effective vaccine. We still don’t have a vaccine that can prevent infection, a preventive vaccine, or a therapeutic vaccine where you give it to people who already have the virus that can help them control the infection. A huge amount of research has happened, but we’re still not there yet.

This article originally appeared on Mayo Clinic News Network.

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HIV: Latest Research

HIV research has made remarkable progress since scientists first identified the disease in the 1980s. There are new prevention methods and therapies to extend the lives of those living with the disease. So what does the future hold for HIV research? Here’s a look at what’s on the horizon.

HIV Prevention

Stopping the spread of HIV is an important step toward ending the outbreak of the disease around the world. Today, there are several methods to slow HIV, and scientists are working on new tools.

HIV is constantly evolving into new strains. This makes it hard to develop a vaccine , but scientists are making progress. The National Institutes of Health (NIH) is researching two HIV vaccines and testing them in people around the world. The goal of these vaccines is to turn on an immune response to a wide range of HIV strains.

Another vaccine candidate from IAVI and Scripps Research works by prompting the immune system to turn on in response to different versions and mutations of HIV. Early research results show it’s 97% effective.

Long-acting prevention

Researchers are also working on HIV prevention methods that last for months or even years. They could offer new choices for protecting yourself against the virus or improve products that you already use.

• Vaginal ring: This flexible silicone ring steadily releases the anti-HIV drug dapivirine. You replace it monthly. Women ages 18 to 45 who took part in two large clinical trials lowered their chance of HIV infection by about 30% when using it.
• Injections: The FDA has approved cabotegravir ( Apretude ) to protect you from HIV for as long as 1 to 6 months.  You get it as a shot once every 8 weeks. Studies show it may be just as safe and work better than the daily oral drug emtricitabine /tenofovir.
• Implants: One promising new technology is long-acting implants in your arm. The matchstick-sized implant slowly releases an anti-HIV drug and could offer protection against HIV for 1 year or longer. Several of these implants are in the works but are still in the early stages of development.
• Oral pills: Researchers are also studying a pill that could protect you from HIV for 30 days. Two other HIV prevention pills, Truvada and Descovy , have been around for years, but you take them daily. Research shows that although these drugs lower your chance of getting HIV by anywhere from 74% to 99%, many people aren’t aware of them or are afraid they would be shamed for taking them.
• Monoclonal antibodies: These lab-created immune system proteins may work to prevent HIV. Scientists are looking at how a mix of assorted antibodies could be a tool in long-term HIV prevention and treatment.

HIV Treatment

There’s no cure for HIV, but medicine can help you manage the disease and ward off other health problems. Scientists and drugmakers continue to develop new treatments for people living with HIV , turning their focus to long-acting therapies.

Once-monthly HIV therapy

In January 2021, the FDA approved the first long-acting injectable treatment for adults with HIV. Cabenuva is a combo of two drugs ( cabotegravir and rilpivirine ) that you take as a shot once a month or every two months. It’s considered a breakthrough in treatment since most HIV drugs require an oral daily dose.

One small survey of people living with HIV shows that more people prefer long-acting shots than pills you take every day. Most (73%) who responded to the survey said they were definitely or probably interested in trying an injectable. This type of medicine could help with issues of missed doses and medical privacy.

Twice Yearly HIV Treatment

Lenacapavir ( Sunlenca ) is the first of a new class of drugs called capsid inhibitors to be FDA-approved and is for treating adults with HIV that is not adequately controlled by their current treatment regimen. It blocks the HIV virus’ protein shell called the capsid which interrupts an important step in the virus life cycle. Sunlenca’s starting dose is given as oral tablets and subcutaneous injections which is followed by maintenance injections every six months. It is given in combination with other antiretroviral(s). 

Other HIV treatments

The FDA has also recently approved two other drugs to treat HIV in kids and adults.

• Dolutegravir ( Tivicay ) for children: There are 1.8 million children (birth to 14 years old) living with HIV. This drug is the first integrase inhibitor (a class of anti-HIV drugs) dissolved in water that’s available for children as young as 4 weeks old.
• Fostemsavir ( Rukobia ): This medicine is an attachment inhibitor (antiretroviral drug) for adults who haven’t had success with other HIV treatments .

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• Review Article
• Published: 01 December 2021

Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021

• Steven G. Deeks 1 ,
• Nancie Archin 2 ,
• Paula Cannon   ORCID: orcid.org/0000-0003-0059-354X 3 ,
• Simon Collins 4 ,
• R. Brad Jones 5 ,
• Marein A. W. P. de Jong 6 ,
• Olivier Lambotte 7 ,
• Rosanne Lamplough 8 ,
• Thumbi Ndung’u 9 , 10 , 11 ,
• Jeremy Sugarman   ORCID: orcid.org/0000-0001-7022-8332 12 ,
• Caroline T. Tiemessen   ORCID: orcid.org/0000-0002-0991-1690 13 ,
• Linos Vandekerckhove   ORCID: orcid.org/0000-0002-8600-1631 14 ,
• Sharon R. Lewin   ORCID: orcid.org/0000-0002-0330-8241 15 , 16 , 17 &

The International AIDS Society (IAS) Global Scientific Strategy working group

Nature Medicine volume  27 ,  pages 2085–2098 ( 2021 ) Cite this article

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• Translational research

Despite the success of antiretroviral therapy (ART) for people living with HIV, lifelong treatment is required and there is no cure. HIV can integrate in the host genome and persist for the life span of the infected cell. These latently infected cells are not recognized as foreign because they are largely transcriptionally silent, but contain replication-competent virus that drives resurgence of the infection once ART is stopped. With a combination of immune activators, neutralizing antibodies, and therapeutic vaccines, some nonhuman primate models have been cured, providing optimism for these approaches now being evaluated in human clinical trials. In vivo delivery of gene-editing tools to either target the virus, boost immunity or protect cells from infection, also holds promise for future HIV cure strategies. In this Review, we discuss advances related to HIV cure in the last 5 years, highlight remaining knowledge gaps and identify priority areas for research for the next 5 years.

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Modern antiretroviral regimens can effectively block HIV replication in people with HIV for decades, but these therapies are not curative and must be taken for life. However, there is evidence that a cure can be achieved; initially, this came from a single case study (Timothy Brown, a man living with HIV who became widely known as the ‘Berlin patient’) following bone-marrow transplantation from a donor who was naturally resistant to HIV 1 . On the basis of this inspiring development and the recognition that not everyone can access and/or adhere indefinitely to antiretroviral therapy (ART), a global consensus emerged approximately 10 years ago that a curative intervention was a high priority for people with HIV and would be necessary to bring an end to the HIV pandemic. Since then, there has been a second case report of a cure following bone-marrow transplantation 2 as well as evidence of persistence of only defective forms of the virus in certain patients 3 and enhanced immune control of the virus by others after only a short time on ART 4 —further supporting the notion that a cure for HIV can be achieved.

An HIV cure includes both remission and eradication. Here, we define the term remission as durable control of virus in the absence of any ongoing ART. Eradication is the complete removal of intact and rebound-competent virus. The minimal and optimal criteria for an acceptable target product profile for an HIV cure, including the duration and level of virus control off ART, has recently been developed and published by the International AIDS Society (IAS), following wide consultation with multiple stakeholders 5 .

In 2011 and 2016, the IAS convened expert working groups to outline a strategy for developing an effective and scalable cure 6 , 7 . Since then, significant progress has been made, and the overall agenda has evolved. Here, we assembled a group of experts from academia, industry, and the community (Box 1 ) to evaluate recent progress and to outline cure-related research priorities for the next 5 years. The key recommendations for each component of the strategy are summarized in Box 2 .

Box 1 The Global Cure Strategy—forming a consensus

The Global Cure Strategy was created using a full online process during the COVID-19 pandemic from November 2020 to August 2021. The co-chairs of the initiative identified the major topics which were divided into eight subthemes, each with its own working group, which included a chair, three scientific experts, at least one community member, an IAS Research-for-Cure fellow, and an industry representative. Working groups met at least twice virtually to generate a summary of key advances and recommendations for the next five years. The steering committee consisted of the chairs of each working group, the co-chairs of the cure strategy and a community expert, selected for diversity in geographic background, gender, age, and expertise. We engaged people living with HIV at all levels as well as a wide range of scientific and nonscientific stakeholders.

The Global Cure Strategy was further refined through a broad, online stakeholder consultation, including an online survey, a review by key stakeholders in the field, and interviews with select experts and opinion leaders (more than 25 respondents). The survey received 162 responses, primarily from people working in academia, nongovernmental organizations, and hospitals or research institutions; 11% of respondents were from organizations of people living with HIV, and 4% were from industry. The majority of respondents were working in Africa, followed by Western and Central Europe, North America, and Central and South America. The summary and detailed responses can be found here: https://www.surveymonkey.com/results/SM-7YYFTZ599/.

Box 2 Key research goals to be addressed in the next 5 years

Understanding hiv reservoirs.

Define and characterize the sources of the replication- and rebound-competent viruses during ART

Define the phenotype of cells harboring intact HIV genomes

Define the clinical significance of defective yet inducible proviruses

Define the mechanisms of clonal proliferation

Determine if infected cells that persist on ART are resistant to cell death

Define the impact of sex and other factors on the reservoir and virus-specific therapies

HIV reservoir measurement

Develop and validate a high-throughput assay to quantify the rebound-competent reservoir

Develop assays that quantify integration sites

Develop assays that account for key qualitative differences in viral transcripts

Develop methods to quantify HIV protein expression in cells and tissues

Develop imaging modalities that quantify the size, distribution, and activity of the reservoir in tissues

Define the link between the cellular reservoirs, residual plasma viremia, and the rebounding virus

Develop assays for point-of-care and eventually at-home viral-load monitoring

Mechanisms of virus control

Identify the mechanisms that contribute to SIV/HIV control

Define the role of HIV-specific antibodies, B cells, and the innate immune response in virus elimination or control

Define the viral dynamics and biomarkers associated with post-treatment control

Optimize human organoid models, as well as mouse and nonhuman primate models, for cure- and remission-related studies

Targeting the provirus

Develop improved strategies to reverse latency

Develop strategies to permanently silence the provirus

Determine the impact of targeting the provirus at the time of initiation of ART

Define the role of viral subtype on the effectiveness of interventions that target the provirus

Targeting the immune system

Develop ‘reduce and control’ approaches

Develop immune modulators

Conduct clinical trials to determine whether combination immunotherapies will result in safe and durable HIV remission

Cell and gene therapy

Define the level of antigen expression needed to enable recognition of infected cells by immunotherapies

Develop gene-editing strategies that target the provirus

Develop strategies for sustained production in vivo of antiviral antibodies

Leverage advances in other biomedical fields to develop safer and more scalable approaches

Pediatric remission and cure

Characterize the establishment, persistence, and potential for preventing or reversing HIV latency in infants and children on ART

Develop assays to monitor and identify biomarkers to predict the efficacy of HIV-1 cure therapeutics

Test HIV immunotherapies and other strategies in infants and children

Social, behavioral, and ethical aspects of cure

Expand community/stakeholder engagement and capacity building

Develop HIV cure research with equity, representation, and scalability considerations

Establish standards for the safe conduct of clinical research

Integrate social, behavioral, and ethics research as part of HIV cure trials

Build capacity for basic discovery research and clinical trials in high-burden, resource-limited settings

A shared definition of the HIV reservoir is crucial for researchers, clinicians, and people living with HIV. Here, we use the term ‘HIV reservoir’ in the context of eradication or remission, as a representative term for all cells infected with replication-competent HIV in both the blood and different anatomical sites in individuals on ART—in other words, all potential sources of viral rebound in the context of a treatment interruption. Although the source of virus rebound is still not entirely understood, we now know that virus can persist in multiple forms, in multiple cells and in multiple sites.

Characterization of the complete HIV reservoir

HIV DNA can be detected in CD4 +  T cells in blood and lymphoid tissue in nearly all people with HIV on ART. These viral genomes are mainly defective. Only a small proportion (less than 5%) appear to be intact and potentially replication-competent 8 . But the HIV reservoir goes beyond circulating CD4 +  T cells; it also includes tissue-resident CD4 +  T cells and cells of the monocyte/macrophage lineage, further complicating efforts to characterize and quantify it. In vitro, HIV preferentially integrates into transcriptionally active genes 9 ; however, in people with HIV on ART, many proviruses (defined as virus that is integrated into the host genome), including intact ones, have been identified in genomic regions that are silent (known as ‘gene deserts’), which limits or precludes their reactivation 3 .

Our initial conception of the HIV reservoir as a static viral archive has given way to a more dynamic view in which, over time on ART, certain within-host HIV variants are gradually eliminated while others persist through various mechanisms, including clonal expansion of infected cells 10 , 11 , 12 , 13 , 14 , 15 . Sporadic infection of new cells during ART has been reported 16 , although there has been no convincing demonstration that viral sequences evolve during effective ART 17 , suggesting that the degree of virus spread is minimal. The sources of viral rebound following cessation of ART are incompletely defined. Multiple factors can contribute to viral replication following ART, including anatomical and microanatomical locations, the infected cell type, cellular phenotype, the nature of the provirus, the antigen specificity of the infected cell, the potential for transcriptional activity given the specific integration site, and/or distribution of antiretroviral drugs within tissues (Fig. 1 ).

The HIV reservoir can be defined across a number of dimensions, including: (1) anatomical and microanatomical locations, (2) cell type (for example, CD4 + T cell or macrophage), (3) cell functional profile (activated or resting; resistance to killing), (4) pool of proviruses with a particular functional profile (for example, interferon-alpha resistant) or (5) triggering event (for example, response to stimulation with a particular antigen), and (6) integration-site features of the rebounding virus.

We recommend prioritizing efforts to understand integration sites of the virus during long-term ART and to understand the inducibility of a provirus on the basis of its chromosomal context. In addition, large prospective studies incorporating analytical treatment interruptions (ATIs) are still needed to probe clinically relevant sources of viral rebound and to identify a biomarker that predicts this. A favorable cure intervention could either prolong the time to the point when virus is detectable (that is, rebound) in plasma or reduce the viral ‘set point’ (that is, post-treatment control).

One of the most daunting obstacles to designing more effective methods to target persistent HIV infection is the lack of biomarkers to unambiguously identify the cells that harbor the rebound-competent reservoir. Recent work has demonstrated that the viral reservoir is preferentially enriched in cells that express programmed death-1 (PD-1) and other immune checkpoint markers, activation markers such as HLA-DR, and chemokine receptors such as CCR6 and CXCR3, but there is no phenotypic marker specific for the reservoir 18 , 19 , 20 , 21 . Specific biomarkers of the reservoir are needed, particularly to assess the impact of cure interventions. Furthermore, understanding how HIV persists in specific tissue sites and relevant local cell populations, such as those in the brain, gastrointestinal tract liver, or genital tract, will be important, given that the mechanism for persistence in each site may be distinct, and therefore different approaches may be required to eliminate each of these reservoirs.

There is growing evidence that some defective proviruses can produce transcripts and proteins (including novel viral RNAs and chimeric viral proteins) that in turn can elicit immune responses and perhaps contribute to chronic inflammation 22 , 23 , 24 , 25 . This may be of high relevance to end organ complications, such as HIV-associated neurological disease 26 . If the production of RNA and proteins from these defective proviruses proves to have clinical relevance, then their removal may be necessary to ensure long-term health.

A major mechanism of HIV persistence is the proliferation of cells that were infected prior to ART, resulting in large clonal populations of infected cells that arise as a result of the site of HIV integration 27 , 28 , response to antigen 29 , 30 , or homeostatic drivers 31 . Characterization of these presumably physiological expansions might lead to the development of therapies aimed at interrupting proliferation of infected cells. It will be important to determine to what degree these expanded clones are transcriptionally active, whether they are an important of post-ART viral rebound, and whether they have some innate survival advantage that prevents the cells from being effectively cleared by the host.

Recent studies have provided some evidence for preferential survival of infected cells with proliferative advantages or with deeper viral latency. Prosurvival and immune-resistance profiles may be particularly important in infected cells that persist despite expression of viral RNA or proteins 32 , 33 , 34 . Opportunities likely exist for collaboration and cross-fertilization of concepts with the cancer field, where the clonal dynamics of tumors have been extensively studied in relation to prosurvival and immune-resistance advantages, such as the work being done on lung cancer through prospective genetic studies in TRACRx ( https://clinicaltrials.gov/ct2/show/NCT01888601 ).

Biological sex can influence HIV pathogenesis, the immune response to HIV infection, and response to antiviral therapy 35 . Furthermore, in some but not all studies, women’s reservoirs have been shown to be less transcriptionally active and less inducible than those of men 36 , 37 , 38 , 39 , 40 . Sex, therefore, is a critical variable that should be considered as new therapies to target the reservoir are developed.

Quantification of the HIV reservoir

Significant progress toward a cure for HIV depends on having sensitive, specific, and quantitative measures of persistent virus that can be applied to various anatomical compartments 41 . Achieving this has been challenging, however, owing to the many sources and heterogeneous properties of persistent, replication-competent HIV. The reservoir can be quantified using assays that measure viral nucleic acid (total and integrated DNA, intact and defective DNA, or different forms of RNA), virus protein (p24), or viral inducibility (by measuring HIV RNA or virus replication following activation in vitro). Each approach has advantages and limitations, and assay outcomes may not always be interchangeable, comparable, or even correlated 8 .

Several groups have developed droplet digital PCR-based assays that discriminate genetically intact proviruses from a large background of defective proviruses, which are slightly less accurate but more high throughput than full genome sequencing 42 , 43 . The application of these assays to large clinical cohorts has demonstrated that there is a modest decrease in the frequency of cells with intact provirus over years on ART 44 , 45 , 46 . These assays have largely been optimized for subtype B virus, the major HIV subtype found in the United States and Europe. Yet there are over ten subtypes worldwide, some of which have evolved different mechanisms for immune evasion and persistence 47 . Pan-subtype-specific assays will need to be developed, and challenges related to cost and scalability remain. Research in this field should ideally culminate in harmonization across laboratories and crossvalidation of results. Future work will need to expand from quantification of virus in blood to quantification in tissue, particularly the more accessible tissues such as lymph nodes and gut mucosa.

Understanding the proviral landscape (defined as the degree of intactness, its transcriptional activity, and its location) is crucial, as these characteristics almost certainly influence the degree to which a provirus will rebound 48 . Over the last decade, several assays have been developed to analyze the exact location at which the virus integrates and whether the integrated virus is intact or defective. The ability to analyze single cells for integration site, viral sequence, and transcription is a major advance 48 ; however, these assays are expensive and low throughput. Technological advances are required to apply this more broadly to clinical samples, including assessment of interventions that target the reservoir.

Cell-associated viral RNA (CA-RNA) provides a measure of the total transcriptional activity of proviruses within a given sample. Several assays have recently been developed that quantify different RNA species, including total, elongated, unspliced, polyadenylated, and multi-spliced RNA, and these stand to give higher-resolution insights into the impact of therapeutic intervention 49 . An important unmet need is to develop approaches to distinguish transcripts arising from defective versus intact proviruses. Another shortcoming hampering broad use of RNA assays is the fact that they are subtype-sensitive. Overall, our ability to study the biology of transcriptionally active proviruses and the role of transcriptional activity as a potential biomarker needs to be further explored.

Since HIV protein expression is also required for recognition by HIV-specific T cells and other immune-based therapies, measuring and characterizing viral proteins in cells and tissues is an important step to understanding HIV persistence and might prove to be a critical determinant for the efficacy of therapies that target the HIV-infected cells directly (for example, chimeric antigen receptor (CAR) T cells or broadly neutralizing antibodies). Quantification of the p24 protein with ultrasensitive enzyme-linked immunosorbent assays can determine the efficacy of therapies that target the reservoir directly. Ultrasensitive p24 assays have emerged as useful tools 25 , but drawbacks include low levels of sensitivity compared with nucleic acid detection, overestimation of the replication-competent reservoir, and the requirement for specialized instrumentation 25 , 50 . Detection of viral envelope protein (the target of many therapeutic interventions for an HIV cure) also remains a challenge. Future strategies should leverage advances in single-cell techniques and new approaches to imaging tissue using super-resolution or expansion microscopy, together with multi-omics approaches.

Substantial progress in other fields of medicine has been made in using advanced imaging techniques to quantify rare diseased cells in tissues. On the basis of some preliminary success in nonhuman primate models 51 , efforts to use radiolabeled HIV-specific tracers and sensitive imaging modalities (for example, positron emission tomography, PET) have been initiated 52 . Similar efforts aimed at characterizing sites of inflammation or expression of specific surface markers that are associated with HIV persistence should also be a priority.

Several studies have attempted to identify sources of rebound virus by probing phylogenetic linkages with the proviral sequences present in various anatomical and cellular compartments. Success has been limited, however, in part owing to the challenging nature of obtaining full-length sequences from the limited number of infected cells in blood or tissue, as well as from plasma with low level viremia 53 . Strategies that can enhance enrichment of infected cells and/or depth of viral sequencing together with high-throughput low-cost single-cell analyses are likely to advance the field. As the RNA in circulating virions is a well-accepted surrogate marker for untreated HIV disease, this measurement could be an effective tool to characterize the rebound-competent population of HIV-infected cells.

Currently, any impact of a therapeutic intervention on the viral reservoir can only be determined with an ATI. A tool for very early detection of viral rebound post-ART using a nonvirological marker—such as measures of the innate immune response 54 —could be very valuable. In addition, better ways to monitor viral load that do not require frequent healthcare appointments will be needed 5 . This should include the development of home-based tests that may not necessarily require high sensitivity as long as testing is performed frequently 55 . Finally, emerging evidence suggests that virus replication during an ATI may be associated with some long-term adverse events 56 , so careful follow up of participants in ATI studies will be necessary.

Mechanisms and models of virus control

Natural control in people living with hiv.

Individuals who naturally control HIV in the absence of any therapy and can maintain a viral load of <50 copies/ml (known as ‘elite’ controllers) have been the focus of intense investigation for years. Research in this area is increasingly focused on those controllers who exhibit remarkably stringent control (‘exceptional’ controllers) 57 , 58 , some of whom might be considered true cures 48 , 59 , and those who became controllers after ART interruption (post-treatment controllers) 60 , 61 . In exceptional controllers, the frequency of infected cells is extremely low, often below the limit of detection of most standard assays for HIV DNA 57 , 59 , there is no intact virus 48 and the site of HIV integration may be distinct 48 ; an agreed definition for an exceptional controller is needed.

Virus-specific CD8 +  T cells targeting particularly vulnerable or conserved epitopes are generally recognized as the key mediator of elite control; such cells are rare in post-treatment controllers and have not yet been characterized in exceptional controllers 4 , 62 . Further characterization of the various controller phenotypes (elite, exceptional, post-treatment) should remain a priority; the identification of unique and potentially informative phenotypes should also be pursued, including individuals on ART who have very small reservoirs 62 . Functional multi-omics studies and emerging single-cell technologies should help to determine the mechanisms involved in exceptional, elite, and post-treatment control. Better animal models of exceptional and post-treatment control would greatly enhance the field, giving access to tissue and the opportunity for longitudinal assessment of virus control 63 .

Virus elimination and control will likely require a coordinated immune response involving more than just T cells. Recent data suggest that autologous antibodies targeting archived viruses as well as interferon sensitivity might influence which virus populations emerge post-ART 54 , 64 , 65 . Studies in simian immunodeficiency virus (SIV)-infected nonhuman primates that naturally control infection have provided indirect evidence that natural killer (NK) cells might be able to effectively control virus in tissues 66 . Better insights into the role of antibodies, natural killer cells, and innate immunity in post-treatment and/or post-intervention control are needed.

The interplay between the virus and immune system during acute infection or immediately after the interruption of ART is largely unknown, at least in humans. During acute infection, those destined to become controllers typically have an initial period of poorly controlled viremia 61 , 67 . For post-treatment controllers, virus control is often achieved more rapidly after cessation of ART than after primary infection 61 , 68 . We need to understand the viral dynamics associated with eventual post-ART control/remission, as this will inform how a treatment interruption should be conducted. It is likely that biomarkers other than the plasma HIV RNA level might allow for the development of safer and more cost-effective strategies for interrupting ART.

Animal models of control

The role of humanized mouse models in cure research is still evolving. Recent studies showing similar effects of latency-reversing strategies in mice and the less scalable nonhuman primate model are encouraging 69 , 70 . Given that access to nonhuman primates for cure studies will likely remain a barrier, ongoing optimization, standardization, and validation of mouse models should be prioritized.

An important discrepancy in translating cure-related findings from SIV-infected nonhuman primates to people with HIV lies in the duration of ART. Although effective ART regimens with integrase inhibitors have been optimized in nonhuman primates, high costs, and treatment-related toxicities necessitate relatively shorter study durations (less than 1–2 years of ART). One possible solution would be for primate research centers to maintain colonies of SIV-infected nonhuman primates receiving very-long-term ART to be directly assigned for studies.

There is ongoing debate about the most appropriate virus to be used in cure-related studies in nonhuman primates. Investigations utilizing broadly neutralizing antibodies or select vaccines directed against the HIV-1 envelope necessitate infection with a virus that expresses HIV envelope proteins (simian-human immunodeficiency virus, SHIV). However, SHIV infections with some strains are characterized by post-treatment control in the absence of any intervention 71 , while others can induce significant disease progression 72 . Therefore, the specific strain used can limit the generalizability of the model. Although SIV infection of nonhuman primates can cause more significant disease progression than HIV infection of people, early ART for SIV infection can limit rapid disease progression and is therefore a useful model for cure studies 73 . Developing immunotherapies that target the SIV envelope in addition to SHIV should also be pursued.

A major recent advance has been the development of genetically barcoded SIV mac239 strains 74 . Because the barcode ‘tags’ are easily quantified and also passed on to progeny virus, this model allows for tracking of clonal dynamics, providing more precise insights into how interventions affect seeding of the reservoir, viral reactivation during ART, or viral recrudescence after ART interruption.

Therapeutic interventions

Since the discovery that HIV can establish a latent infection with minimal HIV transcription, a range of approaches has emerged that specifically target latently infected cells. These include pharmacological modulation of epigenetic or signaling pathways involved in HIV transcription to reactivate latent HIV such that the cells can be targeted and eliminated (‘shock and kill’) or to permanently silence HIV transcription (‘block and lock’) 75 , 76 , 77 . Recent reports have demonstrated that HIV latency is heterogeneous and that latency reactivation is stochastic, implying that a combination of agents targeting various pathways controlling HIV transcription may be necessary to achieve either robust silencing or latency reversal 49 , 78 , 79 , 80 .

A clear limitation of the ‘shock and kill’ approach comes from the discovery that only a fraction of proviruses is intact and among these, only some are inducible by a potent stimulus such as T cell stimulation, let alone by far less potent latency-reversing agents (LRAs) 8 , 81 , 82 , 83 . Furthermore, cells containing reactivated latent HIV may also be relatively resistant to killing by cytotoxic T cells 84 . Complicating the situation even more, CD8 +  T cells appear to suppress HIV transcription and can blunt the effect of LRAs 70 .

Although LRAs tested in humans can induce HIV RNA expression and virion production in vivo, they have failed to reduce the size of the reservoir, even when combined with immunotherapeutic strategies designed to enhance clearance of infected cells 85 , 86 , 87 , 88 , 89 , 90 . This could be due to poor antigen induction by LRAs or insufficient clearance of these targets by immunotherapies (Fig. 2 ). Furthermore, many of the tested LRAs have off-target effects. Newer approaches for delivery of LRAs to reduce toxicity, enhance potency, and improve targeting, potentially leveraging advances in nanomedicine, should be explored. Greater potency could potentially be achieved using LRAs in combination, however, care is needed in these clinical trials, given that unexpected toxicities can emerge—as was recently demonstrated in the evaluation of high-dose disulfiram and vorinostat 91 . Finally, LRAs will likely need to be partnered with therapies that enhance the clearance of cells expressing viral proteins, such as immune-enhancing strategies or proapoptotic drugs 92 .

Reversing latency is an important component of revealing HIV-infected cells, allowing for conversion of a latently infected to a productively infected cell. a , Currently available LRAs reverse latency in only a subset of infected cells, and, when used alone, do not sufficiently eliminate these. b , Enhancing the efficacy of an LRA can be achieved with increased potency, targeted delivery or through using combinations of LRAs. c , Ultimately, depletion of the reservoir will require combining an LRA with other interventions, such as immunotherapy or a proapoptotic drug.

Permanently silencing the HIV promoter by suppressing factors that promote HIV transcription has also emerged as a strategy to target the provirus. The concept is to therapeutically drive HIV into a permanently silenced epigenetic state that resists reactivation (‘deep latency’). The Tat inhibitor didehydro-cortistatin A (dCA) blocks HIV reactivation from human CD4 +  T cells in vitro through epigenetic repression; treatment with dCA in ART-suppressed humanized mouse latency models induces a measurable delay in virus rebound 76 , 93 . Gene therapy can also play an important part in permanent silencing of the provirus using short interfering RNA or other modalities 94 . Thus far, these approaches have yet to be successfully translated into human trials.

Further exploration of the therapeutic potential of permanently silencing the reservoir (‘block and lock’), presumably as part of a combinatorial cure approach, is a high research priority. Some pathways that might be targeted include mTOR, HSF1, and others 95 , 96 , 97 . Efforts to screen for drugs that suppress HIV transcription are encouraged, 96 , 98 , 99 with the goal to rapidly move into preclinical and clinical studies 100 , 101 .

With a recent report indicating that the HIV reservoir is stabilized at the start of ART initiation, efforts should be devised to inhibit this stabilizing effect and/or to enhance reservoir turnover during ART, where such interventions are ideally delivered at ART initiation 102 , 103 , 104 .

Most methods to target the provirus have been developed using subtype B. Thus, while conserved mechanisms govern latency across the different virus subtypes, differences at the level of the promoter may impact responsiveness to various stimuli. Therapies targeting the provirus should be evaluated across multiple HIV subtypes including recombinants.

There is a robust and growing toolbox of immune therapies that might be advanced to proof-of-concept testing. Arguably, the most impactful innovation to date is the isolation and development of broadly neutralizing antibodies for clinical use, but advances have also been made in the development of therapeutic vaccines, vaccine adjuvants, and other immunotherapies. When used in combination in nonhuman primates, these immune therapies have resulted in sustained post-ART control 71 , 105 . When used alone, most of these approaches have had limited effectiveness in people, although some promising results are emerging 88 , 106 , 107 . Combination clinical trials have recently started and are ongoing. Although the combination of either vorinostat or romidepsin (HDAC inhibitors that can increase viral transcription through epigenetic modification) together with different HIV vaccines showed no or minimal reduction in the HIV reservoir 107 , 108 , 109 , results from other studies including a combination of Toll-like receptor agonists, LRAs and broadly neutralizing antibodies are eagerly awaited ( NCT03837756 ; NCT04319367 ; NCT03041012 ).

As it may be challenging to reactivate and eliminate all latently infected cells, or to induce deep irreversible latency in all cells, it seems unlikely that these approaches will be curative by themselves. By reducing the reservoir, however, they might make strategies aimed at controlling the virus long term post-ART more effective. This overall approach of 'reduce and control’ is supported by observations in elite and post-treatment controllers, and theoretical modeling 110 . Multiple approaches that might result in control of a small reservoir are being developed. Assessment of therapeutic vaccines including live vector vaccines such as adenovirus 26, modified vaccine Ankara, and also a cytomegalovirus in nonhuman primate models have been particularly promising, with a subset of animals achieving eradication of virus 71 , 111 . Such studies have not yet been performed in people. Research to develop and test novel immunogen and vaccine designs with broad, potent and durable immunity should be prioritized. Given the recognition that autologous neutralizing antibodies might contribute to reservoir control 64 , novel vaccine approaches aimed at the induction of broadly neutralizing antibodies—including germline targeting 112 —should also be prioritized.

Immune stimulators, immunomodulators, and novel immunotherapies (such as cytokine formulations, Toll-like receptor agonists, immune checkpoint inhibitors or agonists, and novel vaccine adjuvants), used alone or more likely in combination with other approaches, hold promise but have undergone relatively limited testing in HIV-cure studies in people so far 106 , 113 , 114 , 115 .

With the exception of a few anecdotal cases 116 , immunotherapy in people with HIV has yet to recapitulate the promising advances made in nonhuman primates. Combination of various therapies will almost certainly be needed (Fig. 3 ). Conducting such studies is feasible 108 , 117 ; it is expected that initial clinical research will be intensive in nature and designed to identify strategies that might then be tested in well-powered, controlled clinical trials. Defining the mechanisms and potential biomarkers associated with remissions/cures in the preclinical and clinical setting should remain a priority. Determining which combinations to study, and how to define the optimal doses and strategies, poses a significant challenge from a methodological and regulatory perspective. As immunotherapies for HIV move into the clinic, careful attention will have to be paid to immune-related adverse events, including cytokine-release syndrome and autoimmunity.

Strategies that will enhance immune-mediated clearance of latently infected cells include early initiation of ART and the administration of combined interventions at the time of suppressive ART (colored arrows) or during the treatment interruption phase, which will allow for increased antigen presentation. Given that there is no biomarker that can predict viral rebound, analytical treatment interruptions are used to determine whether the intervention has had a clinically meaningful impact. The overarching goal is to either delay viral rebound by at least months or years or reduce the set point of virus replication (that is, the stable level of viral load that the body settles at), preferably to a level of <200 copies/ml. The dashed colored lines represent different potential favorable outcomes from a cure intervention. bNAbs, broadly neutralizing antibodies; LRA, latency reversing agent; TLR, Toll-like receptor.

Cell and gene therapy clinical trials for people with HIV, although safe so far, have been small in scale and with no clear demonstrations of efficacy. The interest in gene therapy for an HIV cure was inspired by the elimination of intact virus in Timothy Brown (also known as the Berlin patient) and Adam Casteljo (also known as the London patient), who both received stem-cell transplants from a CCR5-negative donor 1 , 2 to treat their underlying malignancies. CCR5 is a co-receptor that is needed by most strains of HIV to enter a cell; a reduction in the size of the reservoir has also been reported following stem-cell transplantation to people with HIV from donors who are CCR5-positive 118 , 119 , but the HIV reservoir can’t be completely eliminated, irrespective of the CCR5 status of the donor. In the case of CCR5-negative stem-cell transplantation, the absence of CCR5 in the donor cells is thought to protect the newly transplanted cells from infection, at least with CCR5-dependent HIV strains. Interestingly, in both cases of cure following stem-cell transplantation of CCR5-negative cells, defective virus has been detected, but not intact or replication-competent virus 120 , 121 . These reports have prompted researchers to evaluate CCR5-targeted gene editing as a potentially safer path to cure in people living with HIV on ART, given the high mortality rate and significant morbidity associated with stem-cell transplantation. Timothy Brown unfortunately died in early 2020 owing to recurrence of his leukemia, but remained HIV-free until his death.

Ex vivo gene editing of CCR5 using zinc finger nucleases and re-infusion of CCR5-modified T cells has not yet prevented viral rebound following ATI 122 , 123 , possibly because insufficient cell numbers were engineered and/or engrafted with first-generation editing tools and cell culture protocols and/or because CCR5 disruption alone cannot shift the balance in favor of post-treatment control in the presence of persistently infected cells. More recently, gene therapies have shifted to creating effectors, including chimeric antigen receptor (CAR) T cells, which can recognize and eliminate HIV-infected cells (Fig. 4 ). Other approaches include the use of novel delivery systems to deliver genes to local tissues, resulting in the sustained production of systemically acting antivirals such as broadly neutralizing antibodies 124 , 125 and CD4 mimetics 126 . Finally, attempts are being made to directly target integrated proviruses with technologies such as CRISPR–Cas9 and recombinases 127 , 128 . This approach remains conceptually challenging in view of the disparate locations of latently infected cells, the absence of specific markers to target delivery, the heterogeneity of proviral sequences (the majority of which are defective), and the risk of off-target effects.

Examples of ex vivo (left) and in vivo (right) gene therapy approaches that have been tested in people with HIV on ART. Ex vivo strategies include gene editing to either delete or inactivate CCR5 or HIV provirus in CD4 + -enriched T cells using gene-editing tools such as zinc finger nucelases (ZFN) or CRISPR–Cas9. Alternatively, autologous T cells can be modified to express a CAR that can recognize HIV envelope, and this can then be reinfused into the participant. In vivo strategies, on the other hand, do not require external manipulation of cells; nanoparticles or viral vectors (such as adeno-associated virus (AAV)), which encapsulate mRNA or DNA, respectively, for the relevant gene to be expressed are administered directly to the patient. These approaches have recently been successful using lipid nanoparticles that contain mRNA encoding CRISPR–Cas9 135 or for expression of anti-HIV broadly neutralizing antibodies such as PG9 or VRC07 (ref. 125 ). PBMCs, peripheral blood mononuclear cells; PLWH, person living with HIV.

Many emerging cell and gene therapies are designed to target viral proteins/epitopes that are expressed in abundance on the surface of tumor cells, for example CD19 for the treatment of lymphoma 129 . Various forms of the HIV viral envelope protein (gp120 trimers and monomers, gp41) are expressed on the surface of infected cells, while multiple peptides are presented via HLA molecules. These antigens are expressed at levels well below that of many cancer antigens now being successfully targeted in the clinic. Cell-based therapies such as CAR T cells, once infused into the patient, will only persist and differentiate if there is sufficient antigenic exposure; however, the levels of antigen during ART may be too low 130 . Removal of ART after infusion of CAR T cells (or similar products) could be used to expand these cells in vivo, or more potent latency-reversing agents could be used to enhance envelope protein expression. In addition, novel adjuvants could expand CAR T cells even when the antigen burden is low, as was recently demonstrated in the nonhuman primate model 131 .

The challenges here are primarily those of delivery to relevant cells. In addition to developing methods to target specific cells, which are common problems faced by all potential in vivo gene therapies, targeting latent proviruses also presents the problem of a lack of robust cell surface markers to identify cells harboring such proviruses. Progress in both of these areas will be needed to develop strategies to deliver gene-editing reagents to latently infected cells. Some promising in vivo delivery strategies for CRISPR–Cas9 have included adeno-associated virus to target the SIV virus in nonhuman primates on ART 127 , as well as using engineered CD4 +  cell-homing messenger RNA (mRNA)-containing lipid nanoparticles in mouse models of HIV infection 132 .

Long-term in vivo secretion of antibodies or antibody-like molecules can be achieved following gene therapy vector delivery of antibody cassettes to tissues such as muscle and liver, where enhanced production of antibodies is needed, rather than specific delivery to infected CD4 +  T cells. This can be achieved through direct intramuscular injection leading to uptake in the muscle or, alternatively, intravenous injection, which will allow for uptake in the liver. Ectopic expression of these antibodies in liver or muscle cells fails to recapitulate aspects of natural antibody production, such as responsiveness to antigen and ongoing somatic hypermutation. Therefore, editing the B cell Ig locus itself to express antibodies presents an alternative and attractive gene-editing strategy 133 , 134 .

Sustained production of these antivirals could result in sustained (perhaps lifelong) control of the virus. Many barriers to success exist. Antidrug antibodies that target and clear the vectors often form rapidly 125 , limiting the ability to deliver multiple doses. Advances in mRNA encapsulation within lipid nanoparticles may potentially revolutionize delivery of gene therapy, allowing for delivery of mRNA encoding CRISPR–Cas9 and related guide RNAs in vivo, as has recently been successfully demonstrated in the treatment of transthyretin amyloidosis 135 . Also, antibodies targeting multiple antigens will likely need to be produced at high levels to prevent virus replication and escape.

Advances in T cell manufacturing are expected, driven by cancer CAR T cell therapies, which will also benefit HIV therapies. Similarly, advances occurring in gene therapy treatments for genetic diseases, such as hemoglobinopathies, are catalyzing safer and nongenotoxic conditioning for HSPC transplants, for example based on drug–antibody conjugates. Practicality will also be enhanced by moving toward using allogeneic off-the-shelf products.

Gene and cell therapies now require a shift towards a practical focus, identifying ways to expand use, reduce costs, and allow deployment in resource-limited settings. This could be achieved through abbreviated ex vivo cell manufacturing, including automated closed-system devices (‘gene therapy in a box’), to produce product in a place-of-care setting 136 . While still in the early stages of development, in vivo gene therapy also presents exciting possibilities to significantly expand access by eliminating the need for external manipulation of cells and associated technological requirements.

The unique context of perinatal HIV infection necessitates pediatric-specific strategies to achieve ART-free remission in children. The case of the Mississippi child, who started therapy ~30 hours after birth and achieved remission off ART for 27 months before virus rebounded 137 , 138 , raised the possibility that remission for children can be attained. Subsequent reports of early-treated pediatric cases with long-term (>12 years) virological control off ART have provided examples of post-treatment control in children 139 , 140 .

The nature of the reservoir in children is unique from that in adults. For example, naive CD4 +  T cells are a more important reservoir for the virus in children 141 , 142 . Further development of infant nonhuman primate models for evaluating ART and cure strategies will contribute to our understanding of the HIV reservoir and how to target it in the unique setting of infancy and immune development, but an understanding of the limitations of this model is also crucially important 141 , 142 , 143 , 144 , 145 .

Many of the recent advances in understanding HIV persistence during ART in adults, including frequency and transcriptional activity of intact virus, clonal expansion, sites of proviral integration, and inducibility, need to be applied to studies of children. Optimizing methods that can be adapted to small blood volumes are also needed.

In the context of childhood infection, clarity is needed on how latency is established in naive T cells, susceptibility of these cells to latency reversal, propensity for T cells to clonally expand, and the relative contribution of clonally expanded cells to viral rebound following cessation of ART. It is still unclear whether integration sites and reactivation potential are different in children, and whether these change with age. Given that initial studies suggest a less-inducible reservoir in cases of perinatal infection 146 , it is especially important to determine how to maximize latency reversal in children. The optimal timing of these interventions (for example, at the time of early ART initiation) could potentially limit the pool of infected cells that persist on ART; such approaches can be explored in a nonhuman primate model.

As in adults, better tools are needed to assess the impact of cure interventions in children, including quantification of HIV persistence and in-depth cellular immune profiling. There is a particular need for noninvasive tools, such as total body imaging, to assess central nervous system and other tissue-based reservoirs. It will also be important to identify biomarkers for post-treatment control, including the degree of reduction or alteration in the composition of the latent reservoir that may be predictive of pediatric remission or cure 147 . Finally, preclinical studies in infant nonhuman primates that test new interventions to reduce or eliminate persistent HIV and/or induce viral remission after ART interruption are needed to inform the development of HIV remission and cure intervention strategies. Early therapy alone is insufficient to reliably achieve a cure or long-term remission in children. Novel approaches, including earlier administration and use of more potent antiretroviral drugs, therapeutic vaccines, or other immunotherapeutics, such as broadly neutralizing antibodies and/or innate-immune-enhancing agents, will be necessary.

Research directed toward an HIV cure intertwines critical social, behavioral, and ethical aspects that must be incorporated in the scientific agenda. This research takes place within particular social contexts and communities that shape its permissibility and appropriateness. Accordingly, affected communities must be meaningfully engaged throughout the research process; social and behavioral factors must be interrogated and taken into account because they affect research feasibility, community support for the research, and the well-being of participants and other stakeholders. Research must also address the many ethical issues associated with developing a therapy, particularly since viable options for treatment are already available. Sufficient funding for research toward social, behavioral, and ethical aspects of a cure and for community involvement is therefore essential.

Substantial progress using more conceptual and normative approaches has also been made regarding the ethical issues associated with the interruption of ART 148 , 149 . Similarly, there has been attention focused on acceptable risk thresholds for research 150 . Finally, given the important role of treatment as prevention, efforts have focused on the ethics of partner-protection measures 151 .

Community engagement in HIV cure research is still suboptimal in many settings, being mostly been limited to advisory boards typically comprised of scientifically literate individuals. Capacity to discuss HIV cure research and to evaluate its potential implications for local and global communities must be built within diverse community groups. Communities should be empowered and supported through education and engagement at all levels of the research process to help shape the HIV cure research agenda and allow for potential study participants to have a voice in trial design 152 .

Since HIV cure research is highly complex and nuanced, there is also a need to ensure understanding of it among other key stakeholders, including Institutional Review Boards (IRBs) and clinicians. For example, IRBs need to appreciate the implications of ATIs for partners who they may not see as within their remit, and clinicians need to understand the rationale for ATIs in the research setting.

Attention must focus on broad representation (for example, age, race and ethnicity, gender and sexuality, geographic location, risk behaviors) in research. Diversity in participation is essential during the development of interventions aimed at complete HIV elimination or durable ART-free control. This necessitates research directed at understanding the reasons for under-representation of certain groups of people in HIV cure research. For example, cisgender and transgender women, as well as individuals of some racial and ethnic backgrounds, are less likely to participate in HIV-cure-focused clinical trials 153 . This highlights the need for more nuanced and theoretically engaged research to understand how gender, race, and other characteristics shape engagement with HIV cure research 154 . At the same time, legal and social considerations unique to each context must be identified and addressed. For example, local laws, stigma, and access to healthcare affect research involving the interruption of ART.

There is also a need to better define ethical considerations involved in the selection of populations of interest in which promising cure strategies will be tested. For example, should priority be given to testing new interventions in individuals who initiated treatment during acute infection over those who began treatment during chronic infection? What are the best means to identify and manage the ethical considerations in pediatric HIV cure research? In addition, what measures ought to be taken to ensure that recruitment is not skewed toward people with HIV in resource-limited settings? Further, ethical questions of equity and justice related to the distribution of safe and effective cure interventions must consider acceptability, scalability, and cost-effectiveness. The COVID-19 pandemic has raised unique considerations for research participants, staff, and communities 155 . Given the rapidly changing nature of the pandemic and the availability of COVID-19 vaccines and other treatments, there is a need to continually revise and assess the safety and feasibility of HIV cure research efforts.

During the study design phase, early engagement is needed in communities where research is being considered in order to determine the nature and acceptability of research-related risks. Similarly, stakeholder perceptions should be elicited to guide the development of target product profiles (the minimal and optimal characteristics of a new therapeutic intervention), as recently done for an HIV cure 5 . In especially complex clinical studies, formative research should be used to help develop a robust, informed consent process. Furthermore, nested social and behavioral research (basic, elemental, supportive, integrative) is needed to enhance understanding of the actual experiences of trial participants as well as of sexual partners of participants. These data will help provide a check on current practices, as well as provide a foundation for future efforts aimed at improving them.

Several of the key topics addressed in the previous sections are prerequisites for the development of successful cure strategies and interventions. To date, most HIV cure research has been restricted to high-income countries with relatively low HIV burden and has most often engaged men who have sex with men. HIV strains are genetically and biologically diverse, and host mechanisms of antiviral immunity required for durable control may differ by sex, geography, and ethnicity. Basic discovery research and clinical trials in resource-limited settings must be strengthened and will require enabling infrastructure development and capacity building.

In the next decade, we expect to see a greater understanding of HIV reservoirs, an increasing number of clinical trials and hopefully reports of individuals who achieved long-term remission with less intensive and more widely applicable strategies. On the basis of the current understanding and lessons from ART, it is likely that combinations of these approaches may be the first approach to be implemented. Inclusion of knowledge from fields such as oncology and COVID-19 could also greatly facilitate progress. Finally, open and responsible communication about trials and realistic expectations will remain important. Although safety is the highest priority, with increasing number of clinical trials, there is an increase in the possibility of adverse events which will need to be appropriately managed while allowing the field to advance.

This global scientific strategy, in combination with the recently developed target product profile 5 , will assist with guiding the field toward a widely applicable, acceptable, and affordable cure. The establishment of the HIV Cure Africa Acceleration Partnership 152 will hopefully enable broader engagement and facilitate rapid implementation of any successes into low- and middle-income settings. Fortunately, the resources for such work remain available, and the field is highly committed to making the long-term commitments necessary to develop an effective and scalable remission or cure strategy.

Hutter, G. et al. Long-term control of HIV by CCR5 ∆32/∆32 stem-cell transplantation. N. Engl. J. Med. 360 , 692–698 (2009).

Article   PubMed   Google Scholar  

Gupta, R. K. et al. HIV-1 remission following CCR5∆32/∆32 haematopoietic stem-cell transplantation. Nature 568 , 244–248 (2019).

Article   CAS   PubMed   PubMed Central   Google Scholar  

Jiang, C. et al. Distinct viral reservoirs in individuals with spontaneous control of HIV-1. Nature 585 , 261–267 (2020).

Saez-Cirion, A. et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 9 , e1003211 (2013).

Lewin, S. R. et al. Multi-stakeholder consensus on a target product profile for an HIV cure. Lancet HIV 8 , e42–e50 (2021).

International, A. S. S. W. G. O. H. I. V. C. et al. Towards an HIV cure: a global scientific strategy. Nat. Rev. Immunol. 12 , 607–614 (2012).

Article   CAS   Google Scholar  

Deeks, S. G. et al. International AIDS Society global scientific strategy: towards an HIV cure 2016. Nat. Med. 22 , 839–850 (2016).

Eriksson, S. et al. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog. 9 , e1003174 (2013).

Schaller, T. et al. HIV-1 capsid–cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. PLoS Pathog. 7 , e1002439 (2011).

Cohn, L. B. et al. HIV-1 integration landscape during latent and active infection. Cell 160 , 420–432 (2015).

Lee, G. Q. et al. Clonal expansion of genome-intact HIV-1 in functionally polarized Th1 CD4 + T cells. J. Clin. Investig. 127 , 2689–2696 (2017).

Article   PubMed   PubMed Central   Google Scholar  

Simonetti, F. R. et al. Clonally expanded CD4 + T cells can produce infectious HIV-1 in vivo. Proc. Natl Acad. Sci. USA 113 , 1883–1888 (2016).

Lorenzi, J. C. et al. Paired quantitative and qualitative assessment of the replication-competent HIV-1 reservoir and comparison with integrated proviral DNA. Proc. Natl Acad. Sci. USA 113 , E7908–E7916 (2016).

Bui, J. K. et al. Proviruses with identical sequences comprise a large fraction of the replication-competent HIV reservoir. PLoS Pathog. 13 , e1006283 (2017).

Article   PubMed   PubMed Central   CAS   Google Scholar  

Halvas, E. K. et al. HIV-1 viremia not suppressible by antiretroviral therapy can originate from large T cell clones producing infectious virus. J. Clin. Invest. 130 , 5847–5857 (2020).

Fletcher, C. V. et al. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc. Natl Acad. Sci. USA 111 , 2307–2312 (2014).

McManus, W. R. et al. HIV-1 in lymph nodes is maintained by cellular proliferation during antiretroviral therapy. J. Clin. Invest. 129 , 4629–4642 (2019).

Neidleman, J. et al. Phenotypic analysis of the unstimulated in vivo HIV CD4 T cell reservoir. eLife 9 , e60933 (2020).

Gosselin, A. et al. HIV persists in CCR6 + CD4 + T cells from colon and blood during antiretroviral therapy. AIDS 31 , 35–48 (2017).

Article   CAS   PubMed   Google Scholar  

Fromentin, R. et al. CD4 + T cells expressing PD-1, TIGIT and LAG-3 contribute to HIV persistence during ART. PLoS Pathog. 12 , e1005761 (2016).

Anderson, J. L. et al. Human immunodeficiency virus (HIV)-Infected CCR6 + rectal CD4 + T cells and HIV persistence on antiretroviral therapy. J. Infect. Dis. 221 , 744–755 (2020).

Imamichi, H. et al. Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy. Proc. Natl Acad. Sci. USA 113 , 8783–8788 (2016).

Imamichi, H. et al. Defective HIV-1 proviruses produce viral proteins. Proc. Natl Acad. Sci. USA 117 , 3704–3710 (2020).

Pollack, R. A. et al. Defective HIV-1 proviruses are expressed and can be recognized by cytotoxic T lymphocytes, which shape the proviral landscape. Cell Host Microbe 21 , 494–506(2017).

Wu, G. et al. Gag p24 is a marker of HIV expression in tissues and correlates with immune response. J. Infect. Dis. 224 , 1593–1598 (2021).

Article   PubMed   CAS   PubMed Central   Google Scholar  

Spudich, S. et al. Persistent HIV-infected cells in cerebrospinal fluid are associated with poorer neurocognitive performance. J. Clin. Invest. 129 , 3339–3346 (2019).

Maldarelli, F. et al. HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells. Science 345 , 179–183 (2014).

Wagner, T. A. et al. HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection. Science 345 , 570–573 (2014).

Mendoza, P. et al. Antigen-responsive CD4 + T cell clones contribute to the HIV-1 latent reservoir. J. Exp. Med. 217 , e20200051 (2020).

Simonetti, F. R. et al. Antigen-driven clonal selection shapes the persistence of HIV-1-infected CD4 + T cells in vivo. J. Clin. Invest. 131 , 145254 (2021).

Chomont, N. et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat. Med. 15 , 893–900 (2009).

Ren, Y. et al. BCL-2 antagonism sensitizes cytotoxic T cell-resistant HIV reservoirs to elimination ex vivo. J. Clin. Investig. 130 , 2542–2559 (2020).

Kuo, H. H. et al. Anti-apoptotic protein BIRC5 maintains survival of HIV-1-infected CD4 + T cells. Immunity 48 , 1183–1194(2018).

Cummins, N. W. et al. Maintenance of the HIV reservoir is antagonized by selective BCL2 inhibition. J. Virol. 91 , e00012-17 (2017).

Scully, E. P. Sex differences in HIV infection. Curr. HIV/AIDS Rep. 15 , 136–146 (2018).

Das, B. et al. Estrogen receptor-1 is a key regulator of HIV-1 latency that imparts gender-specific restrictions on the latent reservoir. Proc. Natl Acad. Sci. USA 115 , E7795–E7804 (2018).

Prodger, J. L. et al. Reduced HIV-1 latent reservoir outgrowth and distinct immune correlates among women in Rakai, Uganda. JCI Insight 5 , e139287 (2020).

Falcinelli, S. D. et al. Impact of biological sex on immune activation and frequency of the latent HIV reservoir during suppressive antiretroviral therapy. J. Infect. Dis. 222 , 1843–1852 (2020).

Scully, E. P. et al. Sex-based differences in human immunodeficiency virus type 1 reservoir activity and residual immune activation. J. Infect. Dis. 219 , 1084–1094 (2019).

Szotek, E. L., Narasipura, S. D. & Al-Harthi, L. 17β-Estradiol inhibits HIV-1 by inducing a complex formation between β-catenin and estrogen receptor alpha on the HIV promoter to suppress HIV transcription. Virology 443 , 375–383 (2013).

Abdel-Mohsen, M. et al. Recommendations for measuring HIV reservoir size in cure-directed clinical trials. Nat. Med. 26 , 1339–1350 (2020).

Gaebler, C. et al. Sequence evaluation and comparative analysis of novel assays for intact proviral HIV-1 DNA. J. Virol. 95 , e01986-20 (2021).

Bruner, K. M. et al. Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat. Med. 22 , 1043–1049 (2016).

Peluso, M. J. et al. Differential decay of intact and defective proviral DNA in HIV-1-infected individuals on suppressive antiretroviral therapy. JCI Insight 5 , 132997 (2020).

Gandhi, R. T. et al. Selective decay of intact HIV-1 proviral DNA on antiretroviral therapy. J. Infect. Dis. 223 , 225–233 (2020).

Anderson, E. M. et al. Dynamic shifts in the HIV proviral landscape during long term combination antiretroviral therapy: implications for persistence and control of HIV infections. Viruses 12 , E136 (2020).

Article   PubMed   CAS   Google Scholar  

Sarabia, I. & Bosque, A. HIV-1 latency and latency reversal: does subtype matter? Viruses 11 , 1104 (2019).

Yukl, S. A. et al. HIV latency in isolated patient CD4 + T cells may be due to blocks in HIV transcriptional elongation, completion, and splicing. Sci. Transl. Med. 10 , eaap9927 (2018).

Pardons, M. et al. Single-cell characterization and quantification of translation-competent viral reservoirs in treated and untreated HIV infection. PLoS Pathog. 15 , e1007619 (2019).

Santangelo, P. J. et al. Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques. Nat. Methods 12 , 427–432 (2015).

McMahon, J. H. et al. A clinical trial of non-invasive imaging with an anti-HIV antibody labelled with copper-64 in people living with HIV and uninfected controls. EBioMedicine 65 , 103252 (2021).

De Scheerder, M. A. et al. HIV rebound is predominantly fueled by genetically identical viral expansions from diverse reservoirs. Cell Host Microbe 26 , 347–358(2019).

Mitchell, J. L. et al. Plasmacytoid dendritic cells sense HIV replication before detectable viremia following treatment interruption. J. Clin. Invest. 130 , 2845–2858 (2020).

Draz, M. S. et al. DNA engineered micromotors powered by metal nanoparticles for motion based cellphone diagnostics. Nat. Commun. 9 , 4282 (2018).

Richart, V. et al. High rate of long-term clinical events after ART resumption in HIV-positive patients exposed to antiretroviral therapy interruption. AIDS https://doi.org/10.1097/QAD.0000000000003058 (2021).

Mendoza, D. et al. Comprehensive analysis of unique cases with extraordinary control over HIV replication. Blood 119 , 4645–4655 (2012).

Canoui, E. et al. A subset of extreme human immunodeficiency virus (HIV) controllers is characterized by a small HIV blood reservoir and a weak T-cell activation level. Open Forum Infect. Dis. 4 , ofx064 (2017).

Casado, C. et al. Permanent control of HIV-1 pathogenesis in exceptional elite controllers: a model of spontaneous cure. Sci. Rep. 10 , 1902 (2020).

Namazi, G. et al. The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: posttreatment controllers identified from 14 clinical studies. J. Infect. Dis. 218 , 1954–1963 (2018).

Galvez, C. et al. Extremely low viral reservoir in treated chronically HIV-1-infected individuals. EBioMedicine 57 , 102830 (2020).

Passaes, C. et al. Optimal maturation of the SIV-specific CD8 + T cell response after primary infection is associated with natural control of SIV: ANRS SIC Study. Cell Rep. 32 , 108174 (2020).

Bertagnolli, L. N. et al. Autologous IgG antibodies block outgrowth of a substantial but variable fraction of viruses in the latent reservoir for HIV-1. Proc. Natl Acad. Sci. USA 117 , 32066–32077 (2020).

Gondim, M. V. P. et al. Heightened resistance to host type 1 interferons characterizes HIV-1 at transmission and after antiretroviral therapy interruption. Sci. Transl. Med. 13 , eabd8179 (2021).

Huot, N. et al. Natural killer cells migrate into and control simian immunodeficiency virus replication in lymph node follicles in African green monkeys. Nat. Med. 23 , 1277–1286 (2017).

Madec, Y. et al. Natural history of HIV-control since seroconversion. AIDS 27 , 2451–2460 (2013).

Chun, T. W. et al. Effect of antiretroviral therapy on HIV reservoirs in elite controllers. J. Infect. Dis. 208 , 1443–1447 (2013).

Nixon, C. C. et al. Systemic HIV and SIV latency reversal via non-canonical NF-κB signalling in vivo. Nature 578 , 160–165 (2020).

McBrien, J. B. et al. Robust and persistent reactivation of SIV and HIV by N-803 and depletion of CD8 + cells. Nature 578 , 154–159 (2020).

Borducchi, E. N. et al. Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys. Nature 540 , 284–287 (2016).

Gautam, R. et al. Pathogenicity and mucosal transmissibility of the R5-tropic simian/human immunodeficiency virus SHIV(AD8) in rhesus macaques: implications for use in vaccine studies. J. Virol. 86 , 8516–8526 (2012).

Okoye, A. A. et al. Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound. Nat. Med. 24 , 1430–1440 (2018).

Khanal, S. et al. In vivo validation of the viral barcoding of simian immunodeficiency virus SIV mac239 and the development of new barcoded SIV and subtype B and C simian–human immunodeficiency viruses. J. Virol. 94 , e01420-19 (2019).

Elsheikh, M. M., Tang, Y., Li, D. & Jiang, G. Deep latency: a new insight into a functional HIV cure. EBioMedicine 45 , 624–629 (2019).

Kessing, C. F. et al. In vivo suppression of HIV rebound by didehydro-cortistatin A, a ‘block-and-lock’ strategy for HIV-1 treatment. Cell Rep. 21 , 600–611 (2017).

Margolis, D. M. et al. Curing HIV: seeking to target and clear persistent infection. Cell 181 , 189–206 (2020).

Hosmane, N. N. et al. Proliferation of latently infected CD4 + T cells carrying replication-competent HIV-1: potential role in latent reservoir dynamics. J. Exp. Med. 214 , 959–972 (2017).

Kok, Y. L. et al. Spontaneous reactivation of latent HIV-1 promoters is linked to the cell cycle as revealed by a genetic-insulators-containing dual-fluorescence HIV-1-based vector. Sci. Rep. 8 , 10204 (2018).

Singh, A., Razooky, B., Cox, C. D., Simpson, M. L. & Weinberger, L. S. Transcriptional bursting from the HIV-1 promoter is a significant source of stochastic noise in HIV-1 gene expression. Biophys. J. 98 , L32–L34 (2010).

Cillo, A. R. et al. Quantification of HIV-1 latency reversal in resting CD4 + T cells from patients on suppressive antiretroviral therapy. Proc. Natl Acad. Sci. USA 111 , 7078–7083 (2014).

Laird, G. M. et al. Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations. J. Clin. Invest. 125 , 1901–1912 (2015).

Zerbato, J. M. et al. Multiply spliced HIV RNA is a predictive measure of virus production ex vivo and in vivo following reversal of HIV latency. EBioMedicine 65 , 103241 (2021).

Huang, S. H. et al. Latent HIV reservoirs exhibit inherent resistance to elimination by CD8 + T cells. J. Clin. Investig. 128 , 876–889 (2018).

Gay, C. L. et al. Assessing the impact of AGS-004, a dendritic cell-based immunotherapy, and vorinostat on persistent HIV-1 Infection. Sci. Rep. 10 , 5134 (2020).

Fidler, S. et al. Antiretroviral therapy alone versus antiretroviral therapy with a kick and kill approach, on measures of the HIV reservoir in participants with recent HIV infection (the RIVER trial): a phase 2, randomised trial. Lancet 395 , 888–898 (2020).

Gutiérrez, C. et al. Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy. AIDS 30 , 1385–1392 (2016).

Vibholm, L. et al. Short-course Toll-like receptor 9 agonist treatment impacts innate immunity and plasma viremia in individuals with human immunodeficiency virus infection. Clin. Infect. Dis. 64 , 1686–1695 (2017).

Riddler, S. A. et al. Vesatolimod, a toll-like receptor 7 agonist, induces immune activation in virally suppressed adults with HIV-1. Clin. Infect. Dis. 72 , e815–e824 (2020).

Elliott, J. H. et al. Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV 2 , 17 (2015).

Article   Google Scholar  

McMahon, J. H. et al. Neurotoxicity with high dose disulfiram and vorinostat used for HIV latency reversal. AIDS https://doi.org/10.1097/qad.0000000000003091 (2021).

Kim, Y., Anderson, J. L. & Lewin, S. R. Getting the ‘kill’ into ‘shock and kill’: strategies to eliminate latent HIV. Cell Host Microbe 23 , 14–26 (2018).

Mousseau, G. et al. The tat inhibitor didehydro-cortistatin A prevents HIV-1 reactivation from latency. mBio 6 , e00465 (2015).

Ahlenstiel, C. et al. Novel RNA duplex locks HIV-1 in a latent state via chromatin-mediated transcriptional silencing. Mol. Ther. Nucleic Acids 4 , e261 (2015).

Besnard, E. et al. The mTOR complex controls HIV latency. Cell Host Microbe 20 , 785–797 (2016).

Mori, L. et al. The XPB subunit of the TFIIH complex plays a critical role in HIV-1 transcription and XPB inhibition by spironolactone prevents HIV-1 reactivation from latency. J Virol. 95 , e01247-20 (2020).

Timmons, A. et al. HSF1 inhibition attenuates HIV-1 latency reversal mediated by several candidate LRAs in vitro and ex vivo. Proc. Natl Acad. Sci. USA 117 , 15763–15771 (2020).

Yeh, Y. J. et al. Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation. J. Clin. Invest. 130 , 4969–4984 (2020).

Gavegnano, C. et al. Ruxolitinib and tofacitinib are potent and selective inhibitors of HIV-1 replication and virus reactivation in vitro. Antimicrob. Agents Chemother. 58 , 1977–1986 (2014).

Marconi, V. C. et al. Randomized trial of ruxolitinib in antiretroviral-treated adults with HIV. Clin. Infect. Dis. ciab212 (2021).

Henrich, T. J. et al. Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received solid organ transplantation: A prospective study. Am. J. Transplant 21 , 1765–1779 (2020).

Goonetilleke, N., Clutton, G., Swanstrom, R. & Joseph, S. B. Blocking formation of the stable HIV reservoir: a new perspective for HIV-1 cure. Front. Immunol. 10 , 1966 (2019).

Abrahams, M. R. et al. The replication-competent HIV-1 latent reservoir is primarily established near the time of therapy initiation. Sci. Transl. Med. https://doi.org/10.1126/scitranslmed.aaw5589 (2019).

Brodin, J. et al. Establishment and stability of the latent HIV-1 DNA reservoir. eLlfe 5 , e18889 (2016).

Google Scholar  

Borducchi, E. N. et al. Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys. Nature 563 , 360–364 (2018).

SenGupta, D. et al. The TLR7 agonist vesatolimod induced a modest delay in viral rebound in HIV controllers after cessation of antiretroviral therapy. Sci. Transl. Med. 13 , eabg3071 (2021).

Mothe, B. et al. HIVconsv vaccines and romidepsin in early-treated HIV-1-infected individuals: safety, immunogenicity and effect on the viral reservoir (Study BCN02). Front. Immunol. 11 , 823 (2020).

Leth, S. et al. Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV 3 , e463–e472 (2016).

Conway, J. M. & Perelson, A. S. Post-treatment control of HIV infection. Proc. Natl Acad. Sci. USA 112 , 5467–5472 (2015).

Hansen, S. G. et al. Immune clearance of highly pathogenic SIV infection. Nature 502 , 100–104 (2013).

Steichen, J. M. et al. A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses. Science 366 , eaax4380 (2019).

Rasmussen, T. et al. Impact of anti-PD-1 and anti-CTLA-4 on the HIV reservoir in people living with HIV with cancer on antiretroviral therapy: The AIDS Malignancy Consortium-095 study. Clin. Infect. Dis. 73 , e1973–e1981 (2020).

Riddler, S. A. et al. Vesatolimod, a toll-like Receptor 7 agonist, induces immune activation in virally suppressed adults living with human immunodeficiency virus-1. Clin. Infect. Dis. 72 , e815–e824 (2021).

Papasavvas, E. et al. Safety, immune, and antiviral effects of pegylated interferon alpha 2b administration in antiretroviral therapy-suppressed individuals: results of pilot clinical trial. AIDS Res Hum. Retroviruses 37 , 433–443 (2021).

Mendoza, P. et al. Combination therapy with anti-HIV-1 antibodies maintains viral suppression. Nature 561 , 479–484 (2018).

Colby, D. J. et al. Safety and immunogenicity of Ad26 and MVA vaccines in acutely treated HIV and effect on viral rebound after antiretroviral therapy interruption. Nat. Med. 26 , 498–501 (2020).

Salgado, M. et al. Mechanisms that contribute to a profound reduction of the hiv-1 reservoir after allogeneic stem cell transplant. Ann. Intern. Med. 169 , 674–683 (2018).

Koelsch, K. K. et al. Impact of allogeneic hematopoietic stem cell transplantation on the HIV Reservoir and immune response in 3 hiv-infected individuals. J. Acquired Immune Defic. Syndromes 75 , 328–337 (2017).

Yukl, S. A. et al. Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient. PLoS Pathog. 9 , e1003347 (2013).

Gupta, R. K. et al. Evidence for HIV-1 cure after CCR5∆32/∆32 allogeneic haemopoietic stem-cell transplantation 30 months post analytical treatment interruption: a case report. Lancet HIV 7 , e340–e347 (2020).

Tebas, P. et al. CCR5-edited CD4 + T cells augment HIV-specific immunity to enable post-rebound control of HIV replication. J. Clin. Invest. 131 , e144486 (2021).

Article   CAS   PubMed Central   Google Scholar  

Tebas, P. et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J. Med. 370 , 901–910 (2014).

Martinez-Navio, J. M. et al. Adeno-associated virus delivery of anti-HIV monoclonal antibodies can drive long-term virologic suppression. Immunity 50 , 567–575(2019).

Priddy, F. H. et al. Adeno-associated virus vectored immunoprophylaxis to prevent HIV in healthy adults: a phase 1 randomised controlled trial. Lancet HIV 6 , e230–e239 (2019).

Gardner, M. R. et al. AAV-delivered eCD4-Ig protects rhesus macaques from high-dose SIV mac239 challenges. Sci. Transl. Med. 11 , eaau5409 (2019).

Mancuso, P. et al. CRISPR based editing of SIV proviral DNA in ART treated non-human primates. Nat. Commun. 11 , 6065 (2020).

Karpinski, J. et al. Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity. Nat. Biotechnol. 34 , 401–409 (2016).

Schuster, S. J. et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N. Engl. J. Med. 377 , 2545–2554 (2017).

Herzig, E. et al. Attacking Latent HIV with convertible CAR-T Cells, a highly adaptable killing platform. Cell 179 , 880–894 e810 (2019).

Rust, B. J. et al. Robust expansion of HIV CAR T cells following antigen boosting in ART-suppressed nonhuman primates. Blood 136 , 1722–1734 (2020).

Tombacz, I. et al. Highly efficient CD4 + T cell targeting and genetic recombination using engineered CD4 + cell-homing mRNA-LNPs. Mol. Ther. (2021).

Nahmad, A. D. et al. Engineered B cells expressing an anti-HIV antibody enable memory retention, isotype switching and clonal expansion. Nat. Commun. 11 , 5851 (2020).

Huang, D. et al. Vaccine elicitation of HIV broadly neutralizing antibodies from engineered B cells. Nat. Commun. 11 , 5850 (2020).

Gillmore, J. D. et al. CRISPR–Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385 , 493–502 (2021).

Adair, J. E. et al. Towards access for all: 1st Working Group Report for the Global Gene Therapy Initiative (GGTI). https://doi.org/10.1038/s41434-021-00284-4 (2021).

Persaud, D. et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N. Engl. J. Med. 369 , 1828–1835 (2013).

Luzuriaga, K. et al. Viremic relapse after HIV-1 remission in a perinatally infected child. N. Engl. J. Med. 372 , 786–788 (2015).

Frange, P. et al. HIV-1 virological remission lasting more than 12 years after interruption of early antiretroviral therapy in a perinatally infected teenager enrolled in the French ANRS EPF-CO10 paediatric cohort: a case report. Lancet HIV 3 , e49–e54 (2016).

Violari, A. et al. A child with perinatal HIV infection and long-term sustained virological control following antiretroviral treatment cessation. Nat. Commun. 10 , 412 (2019).

Mavigner, M. et al. Simian immunodeficiency virus persistence in cellular and anatomic reservoirs in antiretroviral therapy-suppressed infant rhesus macaques. J. Virol. 92 , e00562-18 (2018).

Obregon-Perko, V. et al. Simian–human immunodeficiency virus SHIV.C.CH505 persistence in ART-suppressed infant macaques is characterized by elevated SHIV RNA in the gut and a high abundance of intact SHIV DNA in naive CD4 + T cells. J. Virol. 95 , e01669-20 (2020).

Bricker, K. M. et al. Therapeutic vaccination of SIV-infected, ART-treated infant rhesus macaques using Ad48/MVA in combination with TLR-7 stimulation. PLoS Pathog. 16 , e1008954 (2020).

Hessell, A. J. et al. Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques. Nat. Med. 22 , 362–368 (2016).

Shapiro, M. B. et al. Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity. Nat. Commun. 11 , 70 (2020).

Dhummakupt, A. et al. Differences in inducibility of the latent HIV reservoir in perinatal and adult infection. JCI Insight 5 , e134105 (2020).

Article   PubMed Central   Google Scholar  

Hill, A. L. et al. Real-time predictions of reservoir size and rebound time during antiretroviral therapy interruption trials for HIV. PLoS Pathog. 12 , e1005535 (2016).

Julg, B. et al. Recommendations for analytical antiretroviral treatment interruptions in HIV research trials-report of a consensus meeting. Lancet HIV 6 , e259–e268 (2019).

Garner, S. A. et al. Interrupting antiretroviral treatment in HIV cure research: scientific and ethical considerations. J. Virus Erad. 3 , 82–84 (2017).

Protiere, C. et al. Differences in HIV cure clinical trial preferences of French people living with HIV and physicians in the ANRS-APSEC study: a discrete choice experiment. J. Int AIDS Soc. 23 , e25443 (2020).

Peluso, M. J. et al. A collaborative, multidisciplinary approach to HIV transmission risk mitigation during analytic treatment interruption. J. Virus Erad. 6 , 34–37 (2020).

Dybul, M. et al. The case for an HIV cure and how to get there. Lancet HIV 8 , e51–e58 (2021).

Johnston, R. E. & Heitzeg, M. M. Sex, age, race and intervention type in clinical studies of HIV cure: a systematic review. AIDS Res Hum. Retroviruses 31 , 85–97 (2015).

Dube, K. et al . Considerations for increasing racial, ethnic, gender, and sexual diversity in HIV cure-related research with analytical treatment interruptions: a qualitative inquiry. https://doi.org/10.1089/AID.2021.0023 (2021).

Fidler, S. et al. HIV cure research in the time of COVID-19 — antiretroviral therapy treatment interruption trials: a discussion paper. J. Virus Erad. 7 , 100025 (2021).

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Acknowledgements

We acknowledge the generous contribution of all the participants in the working groups, the key opinion leaders who read and provided feedback on the strategy, participants in the online survey and secretarial support from the International AIDS Society. S.R.L. and S.G.D. are funded by National Institutes of Health Delaney AIDS Research Enterprise (DARE) Collaboratory (UM1AI126611 and UM1AI164560). S.R.L. is also funded by the National Health and Medical Research Council (NHMRC; grant number GNT1149990) of Australia and the Australian Centre for HIV and Hepatitis. R.B.J. is funded by the NIH UM1AI64565. C.T.T. is funded by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa (grant 84177). O.L. is funded by the ANRS, Sidaction, University Paris Saclay, Inserm, and CEA (Commissariat à l’Energie Atomique). P.C. is funded by the NIH (HL156247 and AI164561); N.A. is funded by the NIH Delaney CARE Collaboratory 1UM1AI126619 and from R01AI134363; T.N. is funded by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa (grant 64809), The Bill and Melinda Gates Foundation (INV-033558), the International AIDS Vaccine Initiative (UKZNRSA1001) and DFG German-African Network grant (grant number AL 1043/6-1).

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University of California San Francisco, San Fransisco, CA, USA

Steven G. Deeks & Steven Deeks

UNC HIV Cure Center, Department of Medicine, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA

• Nancie Archin

University of Southern California, Los Angeles, CA, USA

• Paula Cannon

HIV i-Base, London, UK

Simon Collins

Weill Cornell Medicine, Cornell University, New York, NY, USA

• R. Brad Jones

Aidsfonds, Amsterdam, the Netherlands

Marein A. W. P. de Jong & Marein de Jong

University Paris Saclay, AP-HP, Bicêtre Hospital, UMR1184 INSERM CEA, Le Kremlin Bicêtre, Paris, France

• Olivier Lambotte

International AIDS Society, Geneva, Switzerland

Rosanne Lamplough

Africa Health Research Institute and University of KwaZulu-Natal, Durban, South Africa

• Thumbi Ndung’u

University College London, London, UK

Ragon Institute of MGH, MIT and Harvard University, Cambridge, MA, USA

Thumbi Ndung’u & Krista Dong

Berman Institute of Bioethics and Department of Medicine, Johns Hopkins University, Baltimore, MD, USA

• Jeremy Sugarman

National Institute for Communicable Diseases and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

• Caroline T. Tiemessen

UZ Ghent, Ghent, Belgium

• Linos Vandekerckhove

Victorian Infectious Diseases Service, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

Sharon R. Lewin

Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Australia

Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

Sharon R. Lewin & Sharon Lewin

UKZN, Durban, South Africa

Zaza Ndhlovu

Centre de Recherche du CHUM and Université de Montréal, Montreal, Canada

Nicolas Chomont

BC Centre for Excellence in HIV/AIDS, Faculty of Health Sciences, Simon Fraser University, Vancouver, Canada

Zabrina Brumme

Sun Yat-sen University, Guangzhou, China

ViiV Healthcare, Branford, CT, USA

Luke Jasenosky

Treatment Action Group, New York, NY, USA

Richard Jefferys

Institut Pasteur, Université de Paris, Unité HIV, Inflammation et Persistance, Paris, France

Aurelio Orta-Resendiz

National Cancer Institute, Center for Cancer Research, Bethesda, MD, USA

Frank Mardarelli

UMC Utrecht, Utrecht, the Netherlands

Monique Nijhuis

Perelmann School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

Katharine Bar & Pablo Tebas

Merck & Co., Inc., Department of Infectious Disease & Vaccines, Kenilworth, NJ, USA

Bonnie Howell

European AIDS treatment group (EATG), Zurich, Switzerland

Alex Schneider

1CONICET – Universidad de Buenos Aires. Instituto de Investigaciones, Biomédicas en Retrovirus y SIDA (INBIRS), Buenos Aires, Argentina

Gabriela Turk

Facultad de Medicina, Departamento de Microbiología, Parasitología e Inmunología, Buenos Aires, Argentina

Makerere University, Makerere, Uganda

Rose Nabatanzi

John Hopkins School of Medicine, Baltimore, MD, USA

Joel Blankson

ICATS, UNC School of Medicine, Chapel Hill, NC, USA

J. Victor Garcia

Emory University School of Medicine, Yerkes National Primate Research Center, Atlanta, GA, USA

Mirko Paiardini

ViiV Healthcare, London, UK

Jan van Lunzen

Chelsea and Westminster Hospital NHS Foundation Trust, London, UK

Christina Antoniadi

Laboratório de AIDS e Imunologia Molecular, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil

Fernanda Heloise Côrtes

Scripps Research Institute, Jupiter, FL, USA

Susana Valente

Aarhus University Hospital, Aarhus, Denmark

Ole S. Søgaard

Universidade Federal de Sao Paulo, Sao Paulo, Brazil

Ricardo Sobhie Diaz

Gladstone Institute of Virology, University of California San Francisco, San Francisco, CA, USA

Melannie Ott

USAHIV Drug Discovery, ViiV Healthcare, Qura Therapeutics, and UNC HIV Cure Center, University of North Carolina at Chapel Hill, Research Triangle Park, NC, USA

Richard (Rick) Dunham

EATG, Berlin, Germany

Siegfried Schwarze

Queen’s University, Kingston, Ontario, Canada

Santiago Perez Patrigeon

MUJHU Care limited, Kampala, Uganda

Josephine Nabukenya

The Rockefeller University, New York, NY, USA

Marina Caskey

IrsiCaixa AIDS Research Institute, HUGTIP, Badalona, Barcelona, Spain

Beatriz Mothe

Chinese Academy of Sciences, National Clinical Research Center for Infectious Diseases, Division of Treatment and Care, National Center for AIDS/STD Control and Prevention, Beijing, China

Fu Sheng Wang

Imperial College London, Department of Infectious Disease, Faculty of Medicine, London, UK

Sarah Fidler

Gilead Sciences, Foster City, CA, USA

Devi SenGupta

European AIDS Treatment Group (EATG), Brussels, Belgium

Stephan Dressler

University of North Carolina Project Malawi, Lilongwe, Malawi

Mitch Matoga

Fred Hutchinson Cancer Research Center, Seattle, WA, USA

Hans-Peter Kiem

Joint Clinical Research Centre, Kampala, Uganda

Cissy Kityo

Caring Cross, Gaithersburg, MD, USA

Boro Dropulic

University of Washington, Seattle, WA, USA

Michael Louella

Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang, Malaysia

Kumitaa Theva Das

Johns Hopkins University School of Medicine, Baltimore, MD, USA

Deborah Persaud

Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA, USA

Ann Chahroudi

University of Massachusetts, Worcester, MA, USA

Katherine Luzuriaga

Chulalongkorn University, Bangkok, Thailand

Thanyawee Puthanakit

ImmunityBio, Inc, Culver City, CA, USA

Jeffrey Safrit

Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana

Gaerolwe Masheto

UNC Gillings School of Global Public Health, Chapel Hill, NC, USA

Karine Dubé

La Trobe University, Melbourne, Australia

Jennifer Power

AVAC, New York, NY, USA

Jessica Salzwedel

VARG, Chiang Mai, Thailand

Udom Likhitwonnawut

UCSD AntiViral Research Center, Delaney AIDS Research Enterprise/UCSF, Palm Springs, CA, USA

Jeff Taylor

Social Policy, Gender Identity, and Sexual Orientation Studies Association (SPoD), University of Lucerne MSc Health Sciences, Istanbul, Turkey

Oguzhan Latif Nuh

Rakai Health Sciences Program, Rakai, Uganda

Edward Nelson Kankaka

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Core Leadership Group

• Steven Deeks
• , Sharon Lewin
• , Marein de Jong
• , Rosanne Lamplough
•  & Simon Collins

Working Group 1 (Understanding HIV reservoirs)

• , Zaza Ndhlovu
• , Nicolas Chomont
• , Zabrina Brumme
• , Luke Jasenosky
• , Richard Jefferys
•  & Aurelio Orta-Resendiz

Working Group 2 (HIV reservoir measurement)

• , Frank Mardarelli
• , Monique Nijhuis
• , Katharine Bar
• , Bonnie Howell
• , Alex Schneider
• , Gabriela Turk
•  & Rose Nabatanzi

Working Group 3 (Mechanisms of virus control)

• , Joel Blankson
• , J. Victor Garcia
• , Mirko Paiardini
• , Jan van Lunzen
• , Christina Antoniadi
•  & Fernanda Heloise Côrtes

Working Group 4 (Targeting the provirus)

• , Susana Valente
• , Ole S. Søgaard
• , Ricardo Sobhie Diaz
• , Melannie Ott
• , Richard (Rick) Dunham
• , Siegfried Schwarze
• , Santiago Perez Patrigeon
•  & Josephine Nabukenya

Working Group 5 (Targeting the immune system)

• , Marina Caskey
• , Beatriz Mothe
• , Fu Sheng Wang
• , Sarah Fidler
• , Devi SenGupta
• , Stephan Dressler
•  & Mitch Matoga

Working Group 6 (Cell and gene therapy)

• , Hans-Peter Kiem
• , Pablo Tebas
• , Cissy Kityo
• , Boro Dropulic
• , Michael Louella
•  & Kumitaa Theva Das

Working Group 7 (Paediatric remission and cure)

• , Deborah Persaud
• , Ann Chahroudi
• , Katherine Luzuriaga
• , Thanyawee Puthanakit
• , Jeffrey Safrit
•  & Gaerolwe Masheto

Working Group 8: (Social, behavioral and ethical aspects of cure)

• , Karine Dubé
• , Jennifer Power
• , Jessica Salzwedel
• , Udom Likhitwonnawut
• , Jeff Taylor
• , Oguzhan Latif Nuh
• , Krista Dong
•  & Edward Nelson Kankaka

Contributions

S.G.D., S.R.L., M.D.J. and R.L. developed the method for generating the strategy and oversaw the governance and establishment of the working groups. All authors on the masthead were members of the steering group. All authors of the IAS Global Scientific Strategy writing group contributed to the writing and approved the submitted version of the manuscript. Members of the IAS Global Scientific Strategy working groups are identified in the list at the end of the manuscript.

Corresponding authors

Correspondence to Steven G. Deeks or Sharon R. Lewin .

Ethics declarations

Competing interests.

S.G.D. receives research support from Gilead and Merck. He is a member of the scientific advisory boards for BryoLogyx, Enochian Biosciences and Tendel. He has consulted for AbbVie, Biotron, Eli Lilly, GSK/ViiV and Immunocore; J.S. is a member of Merck KGaA’s Ethics Advisory Panel and Stem Cell Research Oversight Committee; a member of IQVIA’s Ethics Advisory Panel; a member of Aspen Neurosciences Clinical Advisory Panel; a member of a Merck Data Monitoring Committee; a consultant to Biogen; and a consultant to Portola Pharmaceuticals Inc. None of these activities are related to the issues discussed in this manuscript; T.N. has received research funding from Gilead Sciences; O.L. has been paid expert testimony and consultancy fees from BMS France, MSD, Astra Zeneca; consultancy fees from Incyte, Sobi, grants from ViiV and Gilead; L.V. receives research grants from J&J, ViiV Healthcare and Gilead Sciences; P.C. is a member of Gilead’s HIV Cure Advisory Board; S.R.L.’s institution receives funding for investigator initiated research from Gilead, Merck and Viiv. She has research collaborations with BMS, Abbvie and Merck. She has received honoraria paid to her for membership of advisory boards to Gilead, Merck, Viiv, Immunocore, Vaxxinity, Biotron, Esfam and Abivax; R.L. is an employee of the International AIDS Society; M.d.J. was paid as a consultant by the International AIDS Society. S.C., R.B.J., C.T. and N.A. have no interests to declare.

Additional information

Peer review information Nature Medicine thanks Ravindra Gupta and the other, anonymous, reviewers for their contribution to the peer review of this work. Karen O’Leary was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Deeks, S.G., Archin, N., Cannon, P. et al. Research priorities for an HIV cure: International AIDS Society Global Scientific Strategy 2021. Nat Med 27 , 2085–2098 (2021). https://doi.org/10.1038/s41591-021-01590-5

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Received : 12 September 2021

Accepted : 27 October 2021

Published : 01 December 2021

Issue Date : December 2021

DOI : https://doi.org/10.1038/s41591-021-01590-5

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Gauging attitudes toward a potential HIV vaccine in COVID-19's wake

by The City University of New York

A study by researchers from the CUNY Institute for Implementation Science in Population Health (ISPH) at CUNY SPH, published in the journal AIDS and Behavior , found that gay and bisexual men reported a general willingness to consider a potential HIV vaccine, while expressing concerns about side effects, safety, and potential barriers.

For the study, doctoral candidate Alexa D'Angelo, MPH students Michelle Dearolf, Jennifer MacMartin, and Mathew Elder, Distinguished Professors Christian Grov, Denis Nash, and Sarit Golub of Hunter College used data collected as part of the Together 5,000 study, a U.S. national internet-based cohort study of adult cisgender men, transgender women , and transgender men who were vulnerable to HIV.

The researchers conducted in-depth interviews with non-prep-using men who have sex with men on their perceptions of a potential HIV vaccine.

Participants expressed a spectrum of attitudes towards an HIV vaccine, ranging from enthusiastic support to cautious optimism and skepticism. Positive perceptions were often linked to community-oriented altruism, where individuals felt a sense of duty to protect not only themselves but also their community from HIV.

Concerns about potential side effects and the efficacy of the vaccine were prominent among participants. There was also a notable mistrust in the vaccine development process, which was exacerbated by the experiences and narratives surrounding COVID-19 vaccines.

Participants expressed a desire for specific information about the HIV vaccine, including its safety, efficacy, and the logistics of vaccine administration. They also indicated preferences for how and where they would like to receive this information, emphasizing the need for accessible and trustworthy sources.

"The study highlights the importance of addressing both the motivators and barriers to vaccine acceptance among gay and bisexual men to inform future HIV vaccine implementation efforts," says D'Angelo. "Understanding these perceptions can help tailor communication strategies and interventions to increase vaccine uptake when an HIV vaccine becomes available."

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Breaking New Ground in HIV Research: A SWC Student’s Journey at UCSD Scripps

Barbara Zazueta, a Southwestern College (SWC) student, has made significant strides in HIV research during her time in the Scripps Research Mentorship Program made possible through the Mathematics, Engineering, Science Achievement (MESA) Program at SWC. Over the course of 10 weeks, Zazueta worked on a cutting-edge project focusing on how a key component of the HIV-1 virus assembles, which could be crucial for future treatments.

Barbara’s journey to this point is truly inspiring. Coming from a background where opportunities in scientific research were limited, she has always been passionate about science and determined to make an impact. Her drive led her to excel at SWC, where she found the MESA Program, a supportive community that fueled her ambition. Barbara’s story is a testament to how perseverance, support, and hard work can open doors to incredible opportunities, leading her to contribute to life-changing research.

“Scripps Research has always been one of the places I aspired to be at some point in my studies,” Zazueta shared. “Upon learning that I had been selected, I set my mind on learning as much as possible, making the most of every minute, and being grateful for this opportunity.”

Her project explored how a key part of the HIV-1 virus (called myristoylated Gag) interacts with viral RNA, using advanced imaging techniques to see how these components come together on a simulated cell membrane. This research helps us understand the early steps of HIV assembly, which could be important for developing new treatments.

“Joining a lab and learning something that has been studied for decades, along with mastering techniques that I hadn’t learned at university, was quite challenging for me,” Zazueta admitted. Yet, the support and kindness of her lab colleagues were instrumental in helping her overcome these obstacles.

During her time at Scripps, Zazueta and her team made important discoveries about how the HIV virus begins to build its protective shell, which is crucial for the virus to spread. Their research revealed key early steps in this process, offering new insights that could one day help in developing treatments to prevent the virus from assembling and spreading in the body. 

Zazueta’s’s work has added valuable knowledge to the fight against HIV. Interacting with various professionals and hearing their diverse paths to success provided her with valuable insights and clarity about her own career goals, Zazueta explained, “This opportunity has positively changed my future plans because now I truly know what I want to do… In the future, I aspire to attend graduate school to pursue a PhD in biochemistry. My goal is to engage in research, ideally within an academic setting.”

The MESA Program is a state-wide academic enrichment initiative that supports economically and educationally disadvantaged students, including those historically underrepresented in STEM, to prepare for and excel in math, engineering, and science majors and attain Bachelor’s of Science degrees from four-year institutions.

Director Mourad Mjahed, who oversees the MESA Program emphasized, “Such Undergraduate Research Experiences are crucial to STEM students’ persistence and success.  We are very fortunate to have Scripps Research providing these opportunities to community college students and contributing to the growth and development of their STEM identity. We are equally grateful for increased state funding for the MESA program, which supports stipends for participating students.”

For those interested in joining or learning more about this program, please visit our Mesa Program website .

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Eargo is known for its small,  rechargeable hearing aid devices that are nearly invisible when positioned in the ear canal. Because of the small size, users in verified customer reviews routinely report that they forgot they were there. Also, the unique flexible fibers in Eargo devices mean you won’t get that “plugged up” feeling sometimes caused by in-canal hearing aids.

• Bluetooth capabilities: Yes, all Eargo models offer either Bluetooth connectivity or Bluetooth streaming. Compatible with both iOS 12.0+ and Android 7.0+
• Adjustment:  Remote, phone app, or by tapping your ear
• Noise-canceling technology: Automated noise and feedback cancellation, noise reduction technology in LINK by Eargo, preset hearing settings in Eargo SE, self-fitted noise cancellation settings in Eargo 7.
• Warranty and trial period: Eargo offers a one-year warranty on the Eargo 6, Eargo SE, and LINK by Eargo, and a two-year warranty on the Eargo 7. All warranties include unlimited repairs and a one-time replacement. Eargo also provides a 45-day trial period.
• Financing:  Yes

Our expert take on Eargo

The Eargo 7 features an improved Sound Adjust+ with Clarity Mode, which can automatically adjust the hearing aids’ sound profile to your surroundings for a clearer listening experience in both loud and quiet environments. The Eargo 6 has a similar Sound Adjust feature, but it functions best in quiet environments. While most Eargo hearing aids come with a one-year warranty, the Eargo 7 comes with a longer two-year warranty.

The two newest models, the Eargo SE and LINK by Eargo, are more affordable alternatives to the 6 and 7. The nearly invisible Eargo SE retails for $1,650 and has four customizable hearing settings. The LINK by Eargo has basic features and a lower price tag of $799 per pair. The standout features of LINK by Eargo are Bluetooth 5.3 music/phone streaming and an earbud-style design.

More than 70% of Eargo users who responded to our survey reported that their Eargo hearing aids are comfortable and fit well, which is noteworthy since Eargo only sells online hearing aids, and you don’t need an in-person fitting from a hearing professional. We named Eargo “Best Invisible Fit” because the brand’s devices offer comfort and a small size.

Eargo employs a unique design that allows for a more natural hearing experience with noise reduction and feedback cancellation. The company also offers affordable financing options, with a hearing aid costing as little as $47 a month.

When you purchase an Eargo device, you’ll work with a personal hearing professional to help you along the way, and you’ll have customer support for a lifetime. Eargo hearing aids can be used right out of the box. You can either make adjustments yourself through the smartphone app, or the company’s hearing professionals can help you program your devices remotely.

Read our Eargo review for more information.

MDHearing offers behind-the-ear (BTE) and in-the-canal (ITC) hearing aids to fit almost any budget. That’s important for many customers. Respondents to our Reviews Team’s March 2022 survey of hearing aid users identified cost as the second most important factor when purchasing hearing aids, behind only “ease of set up and use.”

But the real benefit of MDHearing is the company’s versatile line of products. Its four models offer a wide range of features, which is why we gave this brand the title of “Most Feature Options.”

• Bluetooth capabilities: Yes, the VOLT MAX model uses Bluetooth to connect with the MDHearing app for setting and volume adjustments.
• Adjustment:  Volume dial (all models) and remote phone app (VOLT MAX)
• Noise-canceling technology: Noise reduction technology in all models, with advanced noise reduction technology in the Neo SX, and intelligent noise reduction technology and dual directional microphones in the Volt.
• Warranty and trial period: MDHearing offers a one-year warranty on the Air, NEO, NEO XS, and Volt, a two-year warranty on the VOLT MAX, and a 45-day trial period on all models.
• Financing : Yes

Our expert take on MDHearing

All MDHearing models are registered with the U.S. Food and Drug Administration (FDA) and are FDA-cleared. The company’s entry-level model, the AIR, is $297 per pair on sale—one of the lowest prices on this list. It lacks the advanced features of more expensive MDHearing hearing aids, such as dual directional microphones (which help filter out unwanted noise) and Bluetooth capability. But it still comes with advanced noise reduction, rechargeable batteries, feedback cancellation, telecoil technology, and customizable options that make it a good budget-friendly pick.

The water-resistant NEO is often on sale for $297 per pair and has rechargeable batteries, which will give you roughly 18 hours of use on a three-hour charge. The NEO also features background noise reduction and feedback cancellation, simple controls for seamless sound adjustment, and a handy cleaning tool.

The NEO XS has upgraded noise reduction and is the smallest hearing aid in the lineup. It features a completely-in-the-ear design and promises all-day comfort. A standout feature is the portable charging case for convenient, on-the-go recharging. While the NEO XS retails for $1,499, you can often find it on sale for $397 per pair.

The VOLT is a step up in terms of features. In addition to rechargeable batteries, which give you roughly 20 hours on a two-hour charge, the Volt has advanced digital technology with dual directional microphones and intelligent noise reduction, which should improve speech comprehension and, ultimately, easier communication.

At $699.98 on sale ($2,399.98 retail), the VOLT MAX is the most advanced of the line. It may be the priciest, but it comes with the most additional features. To start, it’s the only Bluetooth-compatible model that works with the MDHearing smartphone app, which allows you the extra option to make volume and settings adjustments from your phone—in addition to the manual controls. Plus, the adaptive technology auto adjusts to noise detection. The only downsides are the VOLT MAX is a slightly larger model and the rechargeable battery only lasts 15 hours on a full charge.

If you ever have problems with your devices, MDHearing has licensed audiologists on staff who can answer any questions you have by phone or email. MDHearing doesn’t include hidden costs or equipment fees, so you can be sure the price you see is the true cost. You’ll also get a 45-day money-back guarantee.

Read more in our MDHearing review .

hear.com Horizon hearing aids earned the title “Most Personalized Solution” for its innovative approach to hearing aid technology and user experience. hear.com stands out for its integration of teleaudiology ⓘ A form of telemedicine, hearing care services provided remotely through the use of virtual technology like video, phone, text messaging, and email. and Clinic-in-a-Box service, allowing customers to have their hearing aids professionally programmed and fine-tuned from the comfort of their home.

Clinic-in-a-Box provides everything needed to be fitted with prescription hearing aids, including set-up, customization, and ongoing adjustments, without leaving your home. The box includes a teleaudiology tablet (similar to an iPad) that’s pre-programmed for your appointment, easy-to-use hearing test equipment, and your new hearing aids. The hearing aids are fitted and customized remotely by an audiologist using the results of your hearing test. You then receive ongoing care with further remote adjustments through follow-up video appointments.

While hear.com offers several brands of prescription hearing aids, Horizon is its in-house line. The company makes two models of Horizon hearing aids: the Go IX are mini RIC devices suitable for mild to profound hearing loss, and the Mini IX are tiny ITE devices for mild hearing loss. 

• Battery: Rechargeable, with up to 28 hours of wear time
• B luetooth Capabilities: Yes, streaming for both Apple and Android devices
• Adjustment: On-device button, app, or remote
• Noise-canceling technology: Dual processors adjust speech and environmental noise separately to prioritize speech over background noise, while the Signia Augmented Xperience (AX) technology makes automatic adjustments in noisy environments.
• Warranty and Trial Period: Three-year warranty and 45-day trial period 
• Financing: Yes, they offer flexible financing information
• Insurance: Yes, they work with all major plans

Our expert take on hear.com

Both Horizon models are designed with dual processors, allowing for separate processing of speech and environmental noises. This feature significantly enhances speech understanding in noisy settings like restaurants. The aids also come with an “own voice” processing feature, which minimizes the user’s voice for comfortable listening without compromising the sounds needed to be heard.

The Horizon Go IX model utilizes Signia Augmented Xperience (AX) technology, enhancing speech clarity in challenging environments. Additionally, it comes equipped with advanced features such as speech focus, panorama effect, and relax mode. The design of the Go IX model minimizes thickness at the top of the hearing aid, offering comfort for those who wear glasses or have smaller ears. The slimmer design also contributes to a more discreet appearance than most RIC models.

Both Horizon models come with Clinic-in-a-Box service. 

We are pleased to see hear.com expanding hearing aid access to those for which it was previously out of reach. With the recent rise in the popularity of telehealth, hear.com is at the forefront of an important trend in hearing health care. Telemedicine reached the 80 percent adoption mark in 2022, becoming the preferred method for prescription care and minor illnesses.

 Telemedicine saw a notable rise in use among underserved groups, like people over 55 and people in rural areas. We expect more prescription brands to follow suit in the coming years. 

Lexie offers three self-fitting OTC hearing aids ⓘ Self-fitting hearing aids include software that allows the user to program their own devices. with a range of features. Lexie ties with Jabra and Lucid Hearing for the highest rating from our Reviews Team’s hands-on testing. Given its top score, advanced features, user-friendly app, and competitive price (it’s one of the least expensive hearing aids on this list), Lexie is our Reviews Team’s pick for Most User-Friendly.

• Battery:  Rechargeable and disposable options
• Bluetooth capabilities: Yes, phone call streaming with B2 Plus on iOS only
• Adjustment:  App or buttons on hearing aid
• Noise-canceling technology: Self-fitted environmental settings, including noise and feedback reduction in the Lexie B2 Plus, or you can choose from pre-set environmental settings in the Lexie B1 and Lumen.
• Warranty and trial period:  Lexie offers a one-year manufacturer’s warranty and a 45-day risk-free trial period
• Financing: Lexie doesn’t have traditional financing, but the company now partners with  Klarna , allowing you to have flexible payment options.

Our expert take on Lexie

Lexie hearing aids are appropriate for mild to moderate hearing loss and come with noise reduction and feedback management. They are all available for purchase online and in stores and offer remote support.

The Lumen is a behind-the-ear (BTE) model priced at $799 per pair. It includes disposable batteries and six preset listening profiles. You can make volume or profile adjustments using buttons on the hearing aid or through the smartphone app. The Lumen also has a telecoil, which allows you to stream sounds directly to your hearing aids in any facility equipped with a hearing loop.

The B1 has disposable batteries and costs $799 per pair, while the B2 Plus costs $200 more and comes with rechargeable batteries that last up to 18 hours per charge. The B2 Plus also allows iPhone users to stream calls through their hearing aids. All three Lexie models are self-fitting hearing aids, which give you more control over the settings and sound quality.

The FDA classifies hearing aids as medical devices and regulates them for safety and efficacy. Some manufacturers, such as Lexie and MDHearing, have submitted additional data showing that the settings on certain models can be customized at home by the user. These devices have received FDA clearance as self-fitting hearing aids.

The key difference between a self-fitting hearing aid and a non-self-fitting model is that you can customize the settings to your hearing profile on the former but not the latter. The Lexie B1 and B2 Plus, for example, allow you to use the Lexie app to adjust the volume, bass/treble balance, left/right sound balance, and amount of sound you receive from certain directions. The Lexie Lumen, on the other hand, only lets you change the volume and select from one of six listening settings, but it also adjusts to your hearing loss profile based on an in-app screening that you complete when setting up the hearing aids. In testing, we found the app quick and easy to use.

Read our full Lexie review for more information.

The Audéo Lumity, from prescription hearing aid manufacturer Phonak, comes with high-performance hearing technology, exceptional quality, rechargeable battery life, and Bluetooth connectivity, making it a popular choice for both customers and hearing care professionals. The audiologists our Reviews Team consulted all had positive feedback for Phonak.

• Bluetooth capabilities: Yes, mobile devices supporting Bluetooth, Hands-Free Profile (HFP), and Advanced Audio Distribution Profile (A2DP) should work with your Phonak hearing aids.
• Adjustment:  Local fitting included with purchase
• Noise-canceling technology: AutoSense OS™ 5.0 technology automatically adjusts hearing settings, including background noise, while the SpeechSenor algorithm prioritizes the main speech source for easier conversations.
• Warranty and trial period:  Dependent on retailer
• Financing:  Dependent on retailer

Our expert take on Phonak

Using AutoSense technology , the Audéo Lumity automatically detects your sound environment and adjusts as needed. If you’re in an empty restaurant that suddenly gets busy and the noise around you increases, your Phonak hearing aids will sense the new noise level and make the necessary adjustments with little to no interruption to your hearing ability. You don’t have to press any buttons or pull out your phone.

The Phonak Audéo Lumity also allows you to stream anything from any Bluetooth device. You can even stream from two devices at the same time. You can answer or decline calls with a simple tap of your hearing aid once you’ve connected them to your Bluetooth-enabled smartphone. With hands-free calling, the microphones in the hearing aid double as a phone microphone, so your phone can be in another room, and the person on the other end will still be able to hear you. Phonak hearing aids feature Roger wireless technology , and the Phonak TV Connector allows you to stream television sound directly into your hearing aids.

While the Audéo Lumity offers a variety of features and is suitable for mild to profound hearing loss, it is one of the most expensive hearing aids on this list at $2,600–$6,500 per pair. People with mild to moderate hearing loss who want a simple, easy-to-use device may prefer a more inexpensive over-the-counter option.

Read our Phonak review for more information.

Audicus offers four hearing aid models. Users who purchase the brand’s membership plan can count on receiving free upgrades, dedicated support, and insurance. Audicus also offers several financing options. The company’s flexible payment plans, in partnership with CareCredit and Allegro, make its hearing aids accessible to a wide range of budgets.

• Battery: Rechargeable and disposable options
• Bluetooth capabilities: Yes, audio streaming from up to two Bluetooth devices (not available for the Mini)
• Adjustment: Remote, phone app, buttons on hearing aid, remote control, and mail-in options
• Noise-canceling technology: All models offer automatic adaptation to reduce noise and increase clarity, but the Omni 2 also has smart speech finder technology, so you can hear those close to you in even the noisiest environments.
• Warranty and trial period: Audicus provides a two-year manufacturer’s warranty and a 100-day risk-free trial. Customers enrolled in the membership plan can also receive an unlimited warranty throughout the duration of their membership.
• Financing available: Yes

Our expert take on Audicus

Audicus offers four hearing aid models:

• Spirit 2: RIC-style with telecoil, rechargeable or disposable battery options, Bluetooth compatibility, and upgraded features.
• Omni 2: RIC-style with telecoil, rechargeable or disposable battery options, Bluetooth compatibility, upgraded features, and Speech Finder technology.
• Wave 2: RIC-style with rechargeable or disposable battery options, universal Bluetooth compatibility, automatic noise reduction, and customization from the app.
• Mini: CIC-style, disposable battery only, without telecoil or Bluetooth.

All models are water-resistant and include directional microphones, noise reduction, and customization options. Processing channels vary by model.

Audicus partners with CareCredit and Allegro to offer flexible financing options. CareCredit provides interest-free financing for 12 months, while Allegro caters to different credit scores. Additionally, customers can choose to pay in installments of less than $100 per month over 6, 12, or 18 months.

The Audicus Premier Membership is available for Series 2 Spirit and Omni models and includes new hearing aids every 18 months, accessories, insurance, and dedicated support for a one-time setup fee and monthly subscription. This membership requires a one-time setup fee and monthly fee, though the pricing depends on the exact model of hearing aid you have. Both the Spirit 2 and the Omni 2 require a one-time setup fee of $249 plus a monthly fee of $99 for the Spirit 2 and $119 for the Omni 2.

When purchasing from Audicus, customers can upload their hearing test results or take a free online screening. Audiologists will then custom-program the hearing aids. In-person appointments are available at select locations.

The Signia Silk X is a completely-in-canal (CIC) hearing aid. The small size gives you both an invisible fit and a customized hearing experience. Like other devices on this list, the Signia Silk X does not require an in-person fitting with a hearing professional. It’s actually the only Signia hearing aid that sits completely in your ear canal that doesn’t require an in-person fitting. It uses soft silicone Click Sleeves—these are flexible silicon sleeves that attach to the end of your hearing aids to help position them in your ear canal and provide better acoustics. They come in different sizes based on the size of your ear canal and the type of your hearing loss. The Silk X has 48 channels and six customizable programs, giving you plenty of choices to find the right one for your needs.

• Battery:  Disposable
• Bluetooth capabilities:  No
• Adjustment:  Phone app, remote, or in-person
• Noise-canceling technology: Signia Xperience technology makes noise reduction automatic to the environment, while users can make customized adjustments using the Signia app.
• Warranty and trial period: 2-year warranty on electric components

Our expert take on Signia

Where it really shines is its sound processing. The Signia Silk X runs on the company’s Xperience technology , which uses acoustic-motion sensors to create a more natural sound experience while you move. The Xperience technology is why we called out the Signia Silk X for “Most Natural Sound.” These motion sensors, which are built into the Silk X, detect when the wearer is moving and adapt their sound processing accordingly. This provides a more natural sound than other hearing aids, since we hear differently when we’re moving versus when we’re stationary. Not all hearing aids can account for this difference.

Xperience technology also helps you filter out background noise and focus on the conversations in front of you (for example, in a busy restaurant) and hear a more natural version of your own voice while wearing your hearing aids, according to the company’s whitepaper .

Signia hearing aids are ideal for people with mild to moderate hearing loss, but aren’t suitable for those with moderately severe to profound hearing loss.

Read more in our full Signia hearing aids review .

Most hearing aid manufacturers offer a rechargeable option, but the ReSound Omnia rechargeable hearing aid is one of the most feature-rich and longest lasting, offering up to 30 hours of continued use from three hours of charging. The case also stores and recharges your hearing aids on-the-go without needing to be plugged into an outlet. The long battery life and high customer satisfaction with ReSound rechargeable hearing aids is why we named them the “Best Rechargeable Hearing Aids.”

• Bluetooth capabilities: Yes, streaming of phone calls and music or television with both iOS and Android devices
• Adjustment:  Remote, phone app, or in-person
• Noise-canceling technology: Automatically adjusts to environmental noise and user voice for a realistic hearing experience and omnidirectional listening technology.
• Financing:  Dependent on retailer

Our expert take on ReSound

Rechargeable hearing aids remove the hassle of having to exchange small (and often difficult to swap out) batteries. They also help you potentially save money in the long run since you don’t have to regularly purchase disposable batteries.

ReSound also stands out from other companies for its feature-heavy app. Most hearing aid companies offer apps to help you make minor adjustments to your devices’ settings. But ReSound hearing aids come with an extra level of personalization, including tinnitus management, location-based hearing (which lets you save hearing settings from your favorite locations so your hearing aids automatically switch to those settings when you return), and a “Find My Hearing Aids” feature. You can also use the app to book a ReSound Assist Live Assistance video call, which is a video appointment with a hearing professional for live assistance and remote fine-tuning. Similar to other hearing aid apps, you can also control volume, bass/treble, noise reduction, and microphone direction.

One thing to note is that the ReSound Omnia has one of the most expensive price tags on this list. Rechargeable hearing aids are generally more expensive than those with disposable batteries because rechargeable hearing aids require more advanced technology.

Some OTC hearing aid companies, such as Jabra Enhance, Lexie, Eargo, and Audien, offer rechargeable hearing aids for people with mild to moderate hearing loss at a lower price than ReSound and other prescription brands. Just keep in mind that if your hearing loss is severe or profound, or you’re often in challenging listening environments, a prescription hearing aid like ReSound that offers the most advanced sound processing and in-person support can be worth the extra money.

Brands that didn’t make our best hearing aids list

Our Reviews Team vetted the top hearing aids through careful research and testing, but there are many other brands on the market. While Go Hearing, Otofonix, Rexton, and Unitron are close contenders for our best hearing aids designation, here’s why these brands and others didn’t make our current list.

• Go Hearing : For $199–$499 per pair, Go Hearing OTC hearing aids are a close runner-up to our list because of the brand’s competitive prices and battery life. The brand’s Go Prime discreet ITE model has a long rechargeable battery life of 30 hours and a wireless case that can fully charge your hearing aids up to six times for when you’re on the go, earning a place on our best rechargeable hearing aids roundup.
• Otofonix : Otofonix OTC hearing aids range between $248–$795 per pair. Otofonix hearing aids with rechargeability and Bluetooth connectivity for wireless adjustments tend to be priced higher, with costs varying between models. While Otofonix is relatively low-cost compared to other hearing aid brands on our list, it only offers one BTE style across all six models, while brands like MDHearing offer more versatility at a similar price range of $299–$699 per pair.
• Rexton : You can find Rexton prescription hearing aids at Costco starting at $1,599.99 per pair, or you can purchase them through your audiologist. Offering all hearing aid styles and 14 different models, the brand offers a wide selection of rechargeable devices that treat mild to profound hearing loss. Most Rexton hearing aids offer advanced technology that adapts to your environment to enhance sound and clarify speech, but brands like Starkey have an edge over Rexton with their more advanced, award-winning learning software.
• Unitron : Unitron prescription hearing aids are manufactured by Sonova, the same manufacturer that produces the well-known Phonak hearing aids included in our top picks. This brand offers RIC, BTE, and ITE styles with Bluetooth and rechargeable options that cost from $2,000–$6,000, depending on the model. Although Unitron and Phonak devices closely resemble each other, Phonak has a wider range of accessories and more advanced noise canceling technology.
• Nano : Nano rechargeable OTC hearing aids cost $297–$597 per pair and come in BTE and CIC styles. The Sigma+ ($597) is the only model that offers Bluetooth connectivity to an app for wireless adjustments. This brand’s price range is lower than most, but buyer beware: Nano was involved in a lawsuit over false advertising and misleading business practices for “implying its products are approved by the FDA when they are not” and unlawfully marketing its products for children. Read more in Vermont’s Attorney General 2023 press release , and check out our Nano Hearing Aids Review .
• Nebroo: We don’t recommend Nebroo hearing aids due to their lack of transparency and questionable business practices. The company is quite new, with limited information about its products. Their privacy policy also raises concerns about data sharing and marketing tactics. The limited product details and confusing options further contribute to our reservations about this brand.

Our Reviews Team is always researching and testing new hearing aids, providing our readers with the most up-to-date and accurate information about the quality of both over-the-counter and prescription devices. At this time, our team is testing these hearing aids:

• Zepp Clarity

What is a hearing aid?

A hearing aid is an electronic device designed to improve hearing by making some sounds louder and more clear, allowing a person with hearing loss to better listen and communicate. It works by magnifying sound frequencies entering the ear. Hearing aids come in different styles but always include an element that fits snugly in the ear canal. Companies offer hearing aid devices with different styles, features, and technology to treat different types of hearing loss and and to give users a comfortable experience.

Hearing aids versus cochlear implants

Hearing aids and cochlear implants are designed to assist people with hearing loss, but they function differently and address different types of hearing impairments. Hearing aids are external devices that amplify sounds for individuals with mild to moderate hearing loss. 

Cochlear implants require surgical insertion and are designed for individuals with hearing loss due to severe damage to the inner ear. A cochlear implant is usually recommended after hearing aids fail to clarify speech. The devices bypass damaged parts of the ear and use electrical signals to stimulate the auditory nerve directly.

Hearing aids work by magnifying certain sound frequencies as they enter the ear. 

Hearing aids have one or two microphones to pick up sound, an amplifier to make the sound louder, and a speaker (also called a receiver) to transmit the amplified sound to the middle ear. 

The amount of background noise you hear depends on whether you have an analog or digital hearing aid and how it’s programmed.

Digital vs. analog hearing aids

Hearing aids are available in analog or digital . Although digital is the most common type of device, a few companies still carry analog hearing aids. The difference between analog and digital devices comes down to the type of electronics used. Both devices process sound waves and can be programmed to make certain frequencies louder than others, but the method used sets each type apart. U.S. Food and Drug Administration. Types of Hearing Aids. Found on the internet at https://www.fda.gov/medical-devices/hearing-aids/types-hearing-aids

With an analog hearing aid , you will experience amplification of all sounds, including ambient noise. Some people feel that analog devices provide a more natural hearing experience.

Digital hearing aids convert sound waves to digital signals, providing the clearest hearing possible. These devices can clear out background noise, reduce feedback, and help you focus on the sounds and voices you want to hear. They also offer more complex programming, which allows you to process sounds more selectively.

Types of hearing aids

The six main types of hearing aids—behind-the-ear, receiver-in-canal, in-the-ear, in-the-canal, completely-in-canal, and invisible-in-canal— have their own pros and cons. The right one for you depends on your degree of hearing loss and the types of features you want to prioritize:

• More severe levels of hearing loss require greater amplification and, thus, a larger receiver, which may not fit in the ear canal. This could limit you to a behind-the-ear hearing aid. 
• More technology usually means more microchips or sensors—and they take up space. This is true for Bluetooth streaming and hands-free calling, which are more common in receiver-in-canal or behind-the-ear models because the microchip can be placed in the casing that sits behind the ear.
• Directional microphones don’t work as well on completely-in-canal hearing aids because there’s only one place for the microphone to point—outside the ear canal. Therefore, hearing aids that help you focus on a conversation partner are more likely to be in-the-ear, receiver-in-canal, and behind-the-ear styles.

Here’s a closer look at the six types of hearing aids.

Behind-the-ear (BTE) hearing aid

This device sits behind your ear and includes a plastic tube that hooks over your ear to reach the ear canal. At the end of the tube is a dome or custom-fit ear mold that sits snugly within the canal.

These devices tend to be larger than in-the-ear or in-the-canal hearing aids, but they can offer more capabilities, such as directional microphones, Bluetooth streaming, and a telecoil, which can help you hear better on the telephone and with assisted listening devices. They’re also easier to handle and can be a better choice for people with severe or profound hearing loss because there’s plenty of space in the casing for a larger receiver.

Of the brands and models covered in this review, the following companies offer BTE hearing aids:

Receiver-in-canal (RIC) hearing aid

Also referred to as receiver-in-the-ear (RITE) or mini behind-the-ear (mBTE), RIC devices sit behind the ear like traditional types but are smaller and less visible, especially when you choose one that matches your hair color. They have a tiny wire encased in silicone tubing that hooks over the ear and connects to a small receiver that fits inside the ear canal.

For many users, these devices strike the perfect balance between looks and functionality.

Of the brands and models covered in this review, the following companies offer RIC hearing aids:

• Jabra Enhance

In-the-ear (ITE) hearing aid

This type of hearing aid sits completely within the ear but is larger than the CIC style. ITE hearing aids are generally large enough to offer advanced features such as Bluetooth, directional microphones, and a telecoil, but the smaller size may limit their power compared to BTE models. ITE hearing aids are typically easier to handle and insert than their smaller counterparts, but they may also be more visible.

Of the brands and models covered in this review, the following companies offer ITE hearing aids:

Which is better: In-the-ear or behind-the-ear hearing aids?

The choice between in-the-ear and behind-the-ear hearing aids depends on your individual needs and preferences. Behind-the-ear hearing aids are generally larger and more durable, with longer battery life and more features. They are suitable for all ages and hearing loss levels. In-the-ear hearing aids offer a smaller, more discreet option, often with telecoil compatibility for improved hearing in certain settings.

In-the-canal (ITC) hearing aid

This hearing aid sits deep in the ear canal, but it’s a bit larger and more visible than a CIC device. ITC hearing aids allow for longer battery life than many CIC devices, as well as directional microphones. But they are still susceptible to issues with earwax and moisture, and may be difficult for some people to handle due to their relatively small size.

Completely-in-the-canal (CIC) hearing aid

Also called a mini CIC, this hearing aid is the smallest and least visible device for treating hearing loss. It is positioned completely within the ear canal, and a tiny string allows you to remove the device.

In addition to an invisible fit, CIC devices offer the advantage of less feedback when using a telephone and less disruptive noise from the wind.

Due to their small size, CIC hearing aids may not have some of the features you’d get with other larger devices, such as Bluetooth streaming. Some CIC hearing aids are also too small for a directional microphone. Battery life may also be shorter due to the small size of the device, and ear wax and moisture can affect their function.

Of the brands and models covered in this review, the following companies offer CIC hearing aids:

Invisible-in-canal (IIC) hearing aid

One subtype of CIC hearing aid is the invisible-in-canal (IIC) style. The Phonak Lyric comes in this style. Sitting deep in the second bend of the ear canal, IIC hearing aids are truly invisible when properly inserted. They usually require disposable batteries.

Over-the-counter (OTC) hearing aids

In October 2022, the FDA established a new hearing aids category for OTC hearing aids . As a result, consumers can now purchase certain hearing aids directly from pharmacies, stores, and online retailers—with no doctor visit or prescription required.

Based on the FDA’s final rule , [5] Federal Register. Medical Devices; Ear, Nose, and Throat Devices; Establishing Over-the-Counter Hearing Aids. Found on the internet at https://www.federalregister.gov/documents/2022/08/17/2022-17230/medical-devices-ear-nose-and-throat-devices-establishing-over-the-counter-hearing-aids OTC hearing aids:

• Are “intended to address perceived mild to moderate hearing loss in adults age 18 or older” [6] OTC Hearing Aids: What You Should Know. U.S. Food & Drug Administration. May 3, 2023. Found on the internet at https://www.fda.gov/medical-devices/hearing-aids/otc-hearing-aids-what-you-should-know
• Can be purchased online or in stores without a hearing exam, prescription, or professional fitting

The FDA’s final ruling on OTC hearing aids is meant to increase access. [7] Federal Register. Medical Devices; Ear, Nose, and Throat Devices; Establishing Over-the-Counter Hearing Aids. Found on the internet at https://www.federalregister.gov/documents/2022/08/17/2022-17230/medical-devices-ear-nose-and-throat-devices-establishing-over-the-counter-hearing-aids The high price of hearing aids, the perceived stigma of wearing them, and the concern that they aren’t effective are all common reasons that people with hearing loss wait an average of 10 years before seeking treatment. [8] Smith D, et al. Acceptability, benefits and costs of early screening for hearing disability: a study of potential screening tests and models. Found on the internet at https://www.journalslibrary.nihr.ac.uk/hta/hta11420/#/full-report This has paved the way for more retailers to enter the hearing aid market, which should drive the price down, making them affordable and shortening the wait time before people decide to treat their hearing loss.

Pros and cons of OTC hearing aids

If you’re not sure whether OTC hearing aids are right for you, it’s important to weigh the pros and cons. This can help you make the most informed decision when it comes to treating your hearing loss.

Pros and cons of prescription hearing aids

What to consider before buying a hearing aid.

The National Institute on Deafness and Other Communication Disorders (NIDCD) reports that 37.5 million American adults have some level of hearing loss. [9] National Institute on Deafness and Other Communication Disorders. Quick Statistics About Hearing. Found on the internet at https://www.nidcd.nih.gov/health/statistics/quick-statistics-hearing While hearing loss can occur at any time in life, the problem becomes more common with age.

The NIDCD estimates almost one in four adults between the ages of 65 and 74 and half of people older than 75 have disabling hearing loss. So it may come as a surprise that only one in three adults who could benefit from hearing aids has ever used them. National Institute on Deafness and Other Communication Disorders. Quick Statistics About Hearing. Found on the internet at https://www.nidcd.nih.gov/health/statistics/quick-statistics-hearing

People with hearing loss may not seek help for a variety of reasons, including:

• The cost of hearing aids and hearing care
• The fact that some insurance companies and Medicare plans do not cover hearing aids
• Distance from hearing care providers
• The stigma associated with wearing a hearing aid [10] The Gerontologist. The Stigma of Hearing Loss. Found on the internet at https://academic.oup.com/gerontologist/article/50/1/66/692298

We asked Michelle Brady, an audiologist with Access Audiology , a mobile audiology service in the New York City area, what she’d like people to know about the purchasing process. According to Brady, the most important thing to consider when shopping for a hearing aid is time.

“Research has shown that the longer hearing loss goes untreated, the [more the] brain’s ability to understand and decode speech decreases,” Brady said. “Just like muscles in the body—if you don’t use it, you lose it. Unfortunately, hearing aids cannot override the damage that occurs from years of decreased auditory stimulation. The earlier a patient gets hearing aids and wears them consistently, the better their brain will be able to process and decode speech.”

Hearing loss has also been associated with higher rates of falls, depression, and social isolation among older adults. Getting your hearing checked and corrected can play an important role in improving your quality of life.

What older adults look for in hearing aids

Older adults concerned with the visibility of a hearing aid should consider in-the-ear (ITE) models that are more discreet compared to behind-the-ear (BTE) options. Additionally, if you are not particularly tech-savvy or just want a hearing aid that has the easiest setup, it might be beneficial to consider a more basic hearing aid device without too many complex features. On the other hand, if you’re comfortable with smartphones, apps, and customizing your own settings, a more advanced model does offer more overall convenience in terms of operations.

Hearing aid features to consider

As hearing aid technology changes, more features become available. The following are a few of the most popular additional features that can make your hearing aids more helpful and enjoyable to use.

Common types of hearing loss

The type of hearing loss you have could influence the type of hearing aid you decide to purchase. Read on for information on the most common types of hearing loss . [11] Centers for Disease Control and Prevention. Understanding Hearing Loss. Aug. 7, 2023. Found on the internet at https://www.cdc.gov/ncbddd/hearingloss/parentsguide/understanding/understandinghearingloss.html

• High frequency : Trouble hearing sounds in the 2,000–8,000 hertz (Hz) range, which are many of the sounds involved in speech (most people with age-related hearing loss have problems hearing high frequencies.) This type of hearing loss can make it difficult to hear sounds like “s,” “f,” “t,” and “th,” as well as the vowels “e,” “i,” and “y.” Women’s and children’s voices often fall in this range.
• Low frequency: Difficulty hearing sound frequencies of 2,000 Hz or lower. Lower-frequency hearing loss can affect the perception of sounds like “b,” “d,” “g,” and the vowels “a,” “o,” and “u.” Men’s voices also tend to fall in this range.
• Sensorineural : This is the most common type of age-related hearing loss and is caused by damage to the auditory nerve or hair cells in the inner ear
• Conductive: Caused by a problem with sound traveling through the outer or middle ear
• Presbycusis: Presbycusis is the gradual loss of hearing that occurs as we age
• Mixed : A combination of sensorineural and conductive hearing loss

Degrees of hearing loss

Your degree of hearing loss can also impact the style of hearing aid that suits your needs. The CDC outlines four levels, or degrees, of hearing loss based on how loud sounds must be for you to hear and understand them. [11]

• Mild (26 dB to 40 dB) : Able to hear some speech, but softer sounds are difficult to hear. Those with mid hearing loss may struggle with softer sounds, such as consonants like “s,” “f,” “t,” and “th,” as well as certain vowels like “i.”
• Moderate (41 dB to 55 dB) : Unable to hear most speech at a normal level. With moderate hearing loss, sounds like “n,” “e,” and “u” become harder to hear.
• Severe (56 dB to 90 dB) : Unable to hear speech at all. Those with severe hearing loss can only hear some loud sounds
• Profound (91+ dB) : Profound hearing loss means you are only able to hear extremely loud sounds.

Centers for Disease Control and Prevention. Understanding Hearing Loss. Aug. 7, 2023. Found on the internet at https://www.cdc.gov/ncbddd/hearingloss/parentsguide/understanding/understandinghearingloss.html For mild hearing loss, devices like the Jabra Enhance or Eargo are ideal due to their discreet and comfortable design. Those with moderate hearing loss might prefer the MD Hearing or Lexie, which offer more power and advanced features. 

For severe to profound hearing loss, the Phonak, or Resound provide advanced amplification and technology to significantly improve your hearing and speech understanding.

Hearing aids and tinnitus

Tinnitus is a common condition in which people hear sounds even when no external noise is present. Individuals may experience tinnitus as ringing, whistling, buzzing, or hissing sounds, which may be constant or intermittent. People experiencing hearing loss commonly have tinnitus, resulting from various underlying causes, including exposure to loud noises, ear infections, and age-related auditory decline.

Hearing aids can help you manage tinnitus symptoms, especially when it occurs alongside hearing loss. By amplifying external sounds, hearing aids can make the internal sounds of tinnitus less noticeable, relieving the user. Some hearing aids also have specialized tinnitus masking features that introduce soothing tones or white noise to help distract from the tinnitus sounds. For more information and to explore options tailored to managing tinnitus, visit hearing aids for tinnitus .

How much do hearing aids cost?

The cost of hearing aids largely depends on whether you’re purchasing OTC or prescription hearing aids, as well as the battery type (disposable or rechargeable), features, and sound technology. In fact, hearing aid pricing ranges widely: from $99 to $7,000.

How to find affordable hearing aids

Hearing aids are an investment. Even the most inexpensive hearing aids cost around $300 per pair.

MDHearing, for example, sells budget-friendly digital hearing aids starting at $999.98 per pair (before promotions). Audien offers low-cost devices starting at $99 per pair, but they’re very basic compared to other hearing aids on the market.

Before buying a lower-cost model, make sure to check the fine print. Some retailers and online distributors advertise low-cost hearing aids but are actually selling PSAPs, which amplify sound but do not provide the same level of support or technology as a hearing aid.

Hearing aids are typically sold through hearing care clinics or larger retailers, like Walmart or Costco. But you can also find inexpensive OTC hearing aids online through companies like MDHearing, Jabra Enhance, Lexie, and Eargo.

If you need a prescription hearing aid that’s only offered through a hearing care clinic, consider purchasing through an authorized discount supplier, such as Yes Hearing, which sells high-quality hearing aids, like Phonak and Signia, at a reduced cost. You still work with a local audiologist to get fitted and set up with your device, while the supplier manages the purchasing process with your hearing provider. This option could save you hundreds of dollars.

Read our review of the best affordable hearing aids for more in-depth guidance.

Does Medicare or insurance cover hearing aids?

Medicare Parts A and B don’t include coverage for hearing aids, although many Medicare Advantage Plans (known as Part C) and private insurance plans do provide hearing benefits. Contact your health care provider for more information.

NCOA continues to advocate for Medicare coverage of hearing aids by working with Medicare beneficiary groups and supporting H.R. 5376, the Build Back Better Act , which would initiate Medicare coverage for hearing aids.

In January 2023, U.S. representatives Debbie Dingell (D-MI) and Brian Fitzpatrick (R-PA) also reintroduced H.R. 244, the Medicare Hearing Aid Coverage Act , to Congress. Our Reviews Team spoke with Rep. Dingell’s office and learned that if the bill passes, it would remove a Social Security restriction on hearing aid coverage.

“Hearing aids aren’t a luxury, they are critical for millions of people to maintain a healthy, independent lifestyle. Without them, many seniors cannot interact with family, friends, neighbors, and their communities, and as a result, can become isolated.

“By expanding coverage for hearing aids under Medicare, more seniors will be able to live with dignity and independence. I’m proud to re-introduce this legislation, and remain committed to getting this signed into law to expand access to care for so many who need it. It’s simple: No one should feel isolated, confused, or shut out from the world because they can’t afford hearing aids,” said Dingell.

How to buy hearing aids

A few years ago, there was only one way to get treatment for hearing loss: Make a trip to a hearing care clinic to be tested and fitted for hearing aids. This was a challenge for many people who didn’t have easy access to these locations. But thanks to recent changes in the hearing aids industry, there are now multiple ways to purchase high-quality hearing aids.

Visit a hearing clinic

For prescription hearing aids, you will generally need to visit a hearing care clinic for an in-person consultation and hearing exam by an audiologist or hearing instrument specialist. Audiologists are hearing professionals with at least a master’s degree in the field of audiology who diagnose hearing loss and fit hearing aids. Hearing instrument specialists are hearing professionals with a high school diploma or two-year degree and are only licensed to help fit or program hearing aids.

Purchase prescription hearing aids through a discount network

Another option is to purchase prescription hearing aids from a discount network such as Yes Hearing for up to 40% less than retail price. When you purchase through this network, you’ll be connected with an audiologist in your area for further care. If you are a veteran, check with your local Veteran Affairs (VA) medical center about meeting with an audiologist, getting a hearing test, and determining which hearing aid is right for you.

Larger retail stores, such as Costco, also sell hearing aids. Almost 15% of the hearing aid users we surveyed used Kirkland hearing aids from Costco . The next most popular brand in our survey was Eargo, with 8%.

Buy prescription hearing aids online

The newest way to buy prescription hearing aids is through a company like hear.com. Its Horizon line of hearing aids is offered through a unique Clinic-in-a-Box service, where you are sent everything needed for professional testing, fitting, and customization. All of this is done at home through teleaudiology (virtual hearing care) and with the help of a hearing professional. This system allows people in rural areas or with limited transportation to access high-quality prescription hearing aids.

Understanding prescription hearing aid abbreviations

Each hearing aid company may have its own naming conventions. However, here are some common hearing aid abbreviations and their meanings:

• D = Disposable battery
• R = Rechargeable battery
• T = Telecoil
• S = Standard receiver (for mild hearing loss)
• M = Moderate receiver (for moderate hearing loss)
• P = Power receiver (for severe hearing loss)
• UP = Ultra Power receiver (for profound hearing loss)

Buying OTC hearing aids online

The ability to buy online hearing aids eliminates some of the barriers that can prevent people from seeking care for their hearing loss. Overall, the purchasing process is simple for many OTC hearing aids, but it’s important to know that buying hearing aids online isn’t for everyone.

In some cases, hearing loss may be caused by a medical problem such as diabetes, osteoporosis, or meningitis, and that can only be detected in a consultation with a medical doctor and an audiologist. Buying hearing aids without that intervention may allow an underlying medical problem to persist.

It’s also important to keep in mind that getting the right hearing aid for your needs depends on your specific type and severity of hearing loss. Hearing aids bought through a hearing clinic are programmed individually for each person according to the results of their audiogram (hearing test).

In-person vs. online hearing screenings

In-person hearing tests are much more detailed than online hearing screenings , because they include a physical exam of the ear and several tests to measure your ability to hear and understand various frequencies of speech and sound. Some OTC hearing aid companies, such as Jabra Enhance and Audicus, have an audiology team to interpret audiograms and program hearing aids, but others don’t.

Keep in mind that some of the less expensive devices don’t have the detailed programming options necessary for many types of hearing loss. These include certain OTC hearing aids (including Audien) as well as personal sound amplification products (PSAPs), which are not true hearing aids. PSAPs make all sounds louder, but they aren’t able to target the specific frequencies where hearing loss has occurred or filter out background noise.

If you aren’t sure what type of hearing aid you need, speak with an audiologist or hearing aid specialist who can provide guidance.

Our reviews team interviewed Jacquelyn C. J. Lovitt, a practicing doctor of audiology, to help explain the costs associated with different types of hearing aids.

Buying OTC hearing aids

As mentioned above, many stores that carry health devices also sell OTC hearing aids. Check the list below to see if any of the following retail stores are in your area:

• Victra Verizon

You can also purchase hearing aids online from companies that offer quality OTC hearing devices at lower prices. Some OTC hearing aid manufacturers provide virtual consultations with an audiologist for personalized recommendations and adjustments along with your purchase.

What to expect when you first get hearing aids

Adjusting to new hearing aids often takes time. Here’s what you might experience during the initial adjustment periods:

• Sound sensitivity: It will take your ears some time to warm up to your hearing aids, especially if you’ve had hearing loss for a while. 
• Tinnitus: Some people experience a temporary increase in tinnitus when they first start wearing hearing aids. Often, this is due to an increased awareness of sounds. 
• Difficulty understanding speech: It will take some time to adjust to the different sounds and accents that hearing aids amplify, even if you haven’t had hearing loss for very long. 
• Discomfort: Hearing aids may feel a little uncomfortable at first. It can take some getting used to.

How to care for your hearing aids

Maintaining and taking care of your hearing aids will ensure they function properly and have a long battery life. You should clean your devices regularly, according to the manufacturer’s instructions, as substances like ear wax and fluids, including ear drainage, can cause damage to your hearing aids. You should also avoid moisture (especially if your devices are not water resistant), as well as high temperatures. It’s also best to remove your hearing aids when using hair products. When it comes to battery life, make sure you change disposable batteries as soon as they die and turn off your hearing aids whenever they are not in use.

To ensure your hearing aids function properly and last a long time, remember to:

• Clean the wax filters regularly using a soft-bristled brush
• Inspect and replace ear domes as needed to maintain a comfortable fit
• Wipe down your hearing aids daily with a soft, dry cloth to remove dirt and moisture
• Remove hearing aids before showering, bathing, or swimming, unless they are water-resistant
• Replace disposable batteries quickly to avoid straining the device
• Avoid using harsh chemicals to clean your hearing aids

The future of hearing aids

With so many advances in technology, it’s no surprise the future of hearing aids is especially bright. Manufacturers continue to innovate to offer consumers the best hearing solutions possible through state-of-the-art sound technology.

Newest hearing aid technology in 2024

According to the National Institute on Deafness and Other Communication Disorders, researchers are heavily invested in learning how to apply new signal processing tactics to hearing aids . Additionally, computer-aided technology systems are being utilized to improve design components. New ideations surrounding improved sound transmission and reduced background noise are also underway [13] , as are advancements in ​​enhanced Bluetooth connectivity, rechargeable batteries, and telehealth capabilities for remote adjustments and fittings. National Institute on Deafness and Other Communication Disorders. Hearing Aids. Oct. 11, 2022. Found on the internet at https://www.nidcd.nih.gov/health/hearing-aids

Still, studies focused on how to choose and fit hearing aids for certain groups of people, including children, are in the works, with scientists running directional microphone tests on the ear structure of a tiny fly.

Additionally, the use of Bluetooth connectivity continues to advance with major hearing aid makers because it improves our daily quality of life. Some of the best Bluetooth hearing aids offer multi-device streaming and connectivity so you can switch seamlessly from your smartphone to your television. It won’t be long before more brands implement better Bluetooth features, too. With Bluetooth and smartphones top of mind, we can expect a more upgraded smartphone app experience as well.

Auracast is a revolutionary new technology that allows for simultaneous broadcasting from multiple devices. Traditional Bluetooth connections are limited to a single device. With Auracast, multiple users can listen to the same audio stream at the same time. This technology allows you to share your favorite music or podcasts with friends and families or even listen to public broadcasts directly through your hearing aids.

Plus, well-known hearing aid brands, like Oticon and Widex, are already using artificial intelligence (AI) features for auto-adjustment, user inputs, and to power natural sound. And it won’t be a surprise if big brand collaborations are in store from household names, like Apple and Samsung, which are already extremely sound-oriented.

The rise in popularity of telehealth services now includes hearing health care, too. When it comes to methods of shopping for hearing aids, we expect more companies to begin offering full-service in-home prescription hearing aids to consumers, with models similar to hear.com. 

Hearing aids and health

We know that hearing aids improve the health of users by improving their hearing, but research also suggests that mitigating hearing loss can improve the overall health of older adults. 

The National Institutes of Health’s news publication, NIH Research Matters, [16] NIH Research Matters. Hearing aids slow cognitive decline in people at high risk. Found on the internet at: https://www.nih.gov/news-events/nih-research-matters/hearing-aids-slow-cognitive-decline-people-high-risk reports on the connection between cognitive decline and hearing loss in a new study looking at the connection between hearing aids and slowing cognitive decline. While no significant difference was found in cognitive decline between those who did and did not receive hearing aids when they analyzed the entire population of study participants, a 50% decrease in cognitive decline was seen in those who were at a higher risk of cognitive decline and received a hearing aid.

Falls-related injuries pose a significant health risk for older adults, who are 2.4 times more likely to experience falls if they have hearing loss, according to the Journal of The American Geriatrics Society. In their research, however, they found that consistent use of hearing aids is associated with a 50% decrease in falls compared to those who don’t consistently use hearing aids. 

We also witness a connection between hearing loss and mental health . It’s normal to experience feelings of social isolation or anxiety about communication if your hearing has changed over time, but isolation and communication difficulties can contribute to depression and anxiety. Seeing a doctor about hearing loss, and using hearing aids to improve hearing, can help to mitigate mental health symptoms in those experiencing hearing loss. 

Additional older adult resources

• Best OTC hearing aids
• Best medical alert systems
• Best medical alert systems with fall detection
• Best mattress for back pain
• Best adjustable beds
• Best online will makers

Frequently asked questions

There are five main types of hearing aids:

• Completely-in-canal (CIC) : The smallest type, CIC devices sit completely within the ear canal, with a tiny string that hangs outside your ear so you can remove them easily.
• In-the-canal (ITC) : These devices also sit in the ear canal, but are larger and a bit more visible than CICs.
• Behind-the-ear (BTE): BTE devices have an earmold that rests behind your ear, with a plastic tube that hooks over your ear and runs into your ear canal to transmit amplified sound.
• Receiver-in-canal (RIC): RIC devices, also known as receiver-in-the-ear (RITE) or mini behind-the-ear (mBTE), sit behind the ear like the BTE type, but are often smaller and less visible.
• In-the-ear (ITE): ITE devices sit completely within the ear like the CIC, but are larger, making them easier to handle but more visible.
• Jabra Enhance: Jabra Enhance is a popular choice due to its user-friendly technology and robust customer service.
• Audien: These affordable hearing aids are appreciated for their compact design and sound technology.
• Eargo: Eargo hearing aids are highly regarded for their virtually invisible design and customizable sound settings.
• Lexie: These OTC hearing aids are notable for their user-friendliness and customizable settings.
• Phonak: Phonak is renowned for its cutting-edge technology and extensive range of hearing solutions.

Crackling, or static noise in your hearing aids, usually signals that your devices need maintenance—the battery may be low or there could be a buildup of moisture, earwax, or dirt in your hearing aid. When you hear a crackling, first try repositioning your hearing aids. If that doesn’t work, flush your ear canal with an earwax remover and clean your hearing aids thoroughly. If the problem persists, go to a hearing clinic or contact your device manufacturer for assistance.

Unless a doctor or audiologist has recommended hearing aids, you may not know if you need them. But if you’re noticing that you have trouble hearing in one or both ears, it may be time to consider hearing aids. Your spouse, other family members, and/or friends may have also noticed your difficulties with hearing and recommended hearing aids as a solution.

Some signs of hearing loss to be aware of, according to the Mayo Clinic, include: [14] Mayo Clinic. Hearing Loss. Found on the internet at https://www.mayoclinic.org/diseases-conditions/hearing-loss/symptoms-causes/syc-20373072

• Feeling the need to speak loudly
• Requiring audio devices to be turned up louder than normal
• Asking people to repeat themselves because you can’t hear or understand them
• Straining to hear
• Hearing better out of one ear
• Having difficulty hearing people on the phone
• Noticing that certain sounds and voices are muffled

If you’re experiencing any signs or symptoms of hearing loss, consider seeing an audiologist or hearing specialist. They can conduct a hearing exam to determine the degree of your hearing loss and provide a recommendation for different hearing aid styles and brands.

Even the most advanced hearing aids will not completely restore your hearing to its previous level. Instead, hearing aids are designed to maximize your hearing potential, especially in challenging listening situations.

Although they serve as an excellent tool to help retrain your brain to interpret sounds and filter others out, hearing aids can’t totally restore your hearing.

Hearing aids either use a rechargeable battery that comes with the hearing aid or a standard disposable battery. If the hearing aids use disposable batteries, make a note of the size. In general, standard hearing aid batteries come in four sizes: 10, 13, 312, and 675. You can purchase hearing aid batteries at pharmacies, retail stores, or directly from the hearing aid company.

Most rechargeable batteries are unique to the hearing aid. If you need a new rechargeable battery or charger, buy it directly from your hearing aid company.

You can have hearing loss in one or both ears. But most people have hearing loss in both ears. If you are in this category, experts recommend that you wear bilateral hearing aids —one in your left ear and one in your right ear. [15] Harvard Health Publishing. One Hearing Aid or Two? Found on the internet at https://www.health.harvard.edu/diseases-and-conditions/one-hearing-aid-or-two

Your brain receives signals from both ears, so it’s easier to process the noise into sound if it is getting information from both ears. However, many hearing aids can be programmed separately to accommodate the loss in each ear.

In-the-ear (ITE) hearing aids are custom-made devices designed to fit inside the ear, either partially or completely, and are suitable for individuals with mild to severe hearing loss. These hearing aid styles are less bulky than behind-the-ear (BTE) styles, but still larger and more noticeable than completely-in-the-canal (CIC) hearing aids.

While ITE devices are generally easier to insert, handle, and control than CIC styles, they do require an adjustment period. Some people experience discomfort during the first few weeks of use, often because they are new to wearing hearing aids, but also because they’ve become accustomed to the way other hearing aid styles feel in their ears, especially BTE styles. With time, most people find ITE styles comfortable and easy to wear.

In-the-ear hearing aids may come with a larger variety of features than smaller, nearly invisible devices are able to provide because they have more room for technology inside their casings, like telecoil for enhanced sound during phone conversations and public events. But they also have some drawbacks. ITEs may require more frequent cleaning due to earwax buildup, and are more prone to feedback issues than some models. ITE styles are not recommended for young children or those with profound hearing loss.

Adjusting to your new hearing aids takes time. For some people, getting used to wearing hearing aids happens within a few days. For others, there is an adjustment period that may take a few months.

In general, you should notice a difference right away. If you’re having problems, contact the hearing center or online retailer that sold you the hearing aids. They can provide tips and guidance to help with the fit and improve your hearing aid experience.

All hearing aids work to some degree. The style, size, and features determine how well they work for each type of hearing loss.

The advantage of small hearing aids is the almost invisible appearance they provide. Research shows that many people, especially older adults, associate hearing loss and hearing aids with stigma related to perceived feelings of lower cognitive ability, ageism (that hearing aids or hearing loss make them feel older), and vanity (that hearing aids or hearing loss make them look older).

Because they go in your ear, smaller hearing aids may not be a good fit for everyone’s ear canal. That’s why it’s a good idea to go to a professional to get fitted. Small hearing aids may also require more battery changes since they can only hold a small battery, and the compact size may result in fewer features.

If you buy one single hearing aid, the average cost is about $2,300, with the full range at $1,000–$4,000. For more severe hearing loss, the price of one hearing aid can cost up to $6,000.

Hearing aids are a substantial investment, and finding an affordable hearing device is a high priority for many people. Most companies offer several models at different prices.

If you’re looking for a hearing aid brand that consistently sells lower-priced products, MDHearing and Audien are both great places to start. In general, MDHearing devices range in price from $200–$800 for a single hearing aid and $400–$1,000 per pair. Audien carries even lower-priced hearing devices, ranging from $99–$249 per pair.

Visit NCOA’s Hearing Health page for more resources on hearing health for older adults.

The best hearing aids are those customized to your specific hearing loss, lifestyle, and preferences. Consulting with a hearing care professional, like an audiologist, is crucial to assess your hearing and recommend suitable options that are within your budget. 

Consider your daily environment, occupation, and desired features. The right hearing aid should fit comfortably enough to wear all day. Ultimately, the best hearing aid is one you’re willing to wear consistently, enhancing your daily life without discomfort.

On average, hearing aids last about three to seven years. How well you maintain your hearing aids will impact their lifespan, but it also depends on their construction and how much wear and tear they experience from being worn each day.

Adjusting to hearing aids takes patience. The transition can take a few days to several months, so give yourself time to adapt, and visit your hearing-care professional for adjustments as needed. It’s important to remember that hearing aids aren’t able to restore your hearing to its original state but to enhance it. Hearing professionals advise users to wear their hearing aids as often as possible and in different settings, whether watching TV at home, walking in the neighborhood, or dining in a busy restaurant, to help your brain readjust to the sounds it was missing.

If you find the adjustment period challenging, schedule a follow-up with your hearing specialist. They can tweak your device settings or suggest a different style that better suits your needs. Remember, even a minor adjustment to your hearing aids can make a significant difference in comfort and performance.

Costco hearing aids are often more affordable than other retailers due to Costco’s business model. They can offer lower prices by buying hearing aids in bulk directly from manufacturers. Costco then sells hearing aids to members at a discounted rate. Learn more about the best Costco hearing aids , including features and pricing.

Phonak hearing aids are highly recommended for speech clarity due to advanced sound processing technology and adaptive microphones, which enhance speech understanding in various environments.

The most comfortable hearing aids are typically lightweight, have a discreet design, and use soft, flexible materials that conform to the shape of the ear. Look for features like customizable ear tips and adjustable settings for a personalized fit that also enhances comfort for extended wear​.

Have questions about this review? Email us at [email protected] .

• Centers for Disease Control and Prevention. Facts About Falls. Found on the internet at https://www.cdc.gov/falls/facts.html
• John Hopkins Medicine. Hearing Loss Linked to Three-Fold Risk of Falling. Feb. 27, 2012. Found on the internet at https://www.hopkinsmedicine.org/news/media/releases/hearing_loss_linked_to_three_fold_risk_of_falling
• Rock Health. Consumer Adoption of Digital Health in 2022: Moving at the Speed of Trust. Feb. 21, 2023. Found on the internet at https://rockhealth.com/insights/consumer-adoption-of-digital-health-in-2022-moving-at-the-speed-of-trust/
• U.S. Food and Drug Administration. Types of Hearing Aids. Found on the internet at https://www.fda.gov/medical-devices/hearing-aids/types-hearing-aids
• Federal Register. Medical Devices; Ear, Nose, and Throat Devices; Establishing Over-the-Counter Hearing Aids. Found on the internet at https://www.federalregister.gov/documents/2022/08/17/2022-17230/medical-devices-ear-nose-and-throat-devices-establishing-over-the-counter-hearing-aids
• OTC Hearing Aids: What You Should Know. U.S. Food & Drug Administration. May 3, 2023. Found on the internet at https://www.fda.gov/medical-devices/hearing-aids/otc-hearing-aids-what-you-should-know
• National Institute on Deafness and Other Communication Disorders. Over-the-Counter Hearing Aids. Found on the internet at https://www.nidcd.nih.gov/health/over-counter-hearing-aids
• Smith, D, et al. Acceptability, Benefits and Costs of Early Screening for Hearing Disability: A Study of Potential Screening Tests and Models. November 2007. Found on the internet at https://www.journalslibrary.nihr.ac.uk/hta/hta11420/#/full-report
• National Institute on Deafness and Other Communication Disorders. Quick Statistics About Hearing. Found on the internet at https://www.nidcd.nih.gov/health/statistics/quick-statistics-hearing
• Wallhagen, Margaret. The Stigma of Hearing Loss. The Gerontologist. February 2010. Found on the internet at https://academic.oup.com/gerontologist/article/50/1/66/692298
• Centers for Disease Control and Prevention. Understanding Hearing Loss. Aug. 7, 2023. Found on the internet at https://www.cdc.gov/ncbddd/hearingloss/parentsguide/understanding/understandinghearingloss.html
• Mayo Clinic. Hearing aids: How to choose the right one. Found on the internet at https://www.mayoclinic.org/diseases-conditions/hearing-loss/in-depth/hearing-aids/art-20044116
• National Institute on Deafness and Other Communication Disorders. Hearing Aids. Oct. 11, 2022. Found on the internet at https://www.nidcd.nih.gov/health/hearing-aids
• Mayo Clinic. Hearing Loss. Found on the internet at https://www.mayoclinic.org/diseases-conditions/hearing-loss/symptoms-causes/syc-20373072
• Harvard Health Publishing. One Hearing Aid or Two? Found on the internet at https://www.health.harvard.edu/diseases-and-conditions/one-hearing-aid-or-two
• Source: NIH Research Matters.  Hearing aids slow cognitive decline in people at high risk. Found on the internet at: https://www.nih.gov/news-events/nih-research-matters/hearing-aids-slow-cognitive-decline-people-high-risk