TAG HIV Basic Science, Vaccines, and Cure Project Blog

There were 24 updates to the TAG listing for February 2026, including three newly registered clinical trials.

New Additions

The company BioNTech is launching a phase I trial of BNT351, a new broadly neutralizing antibody (bNAb). Based on a poster (#524) presented at the Conference on Retroviruses and Opportunistic Infections (CROI) yesterday, BNT351 is a modified version of a potent bNAb named 1-18 that was first reported on by the laboratory of Florian Klein in 2020. The modifications introduce “LS” mutations to extend the half-life of the bNAb and allow for less frequent dosing. The CROI poster reports broad neutralization of panel of HIV variants from different clades, and strong activity against a panel of clade C viruses sampled during the Antibody-Mediated Prevention (AMP) trial. Since adding the study to the listing, enrollment has begun at a site in Mannheim, Germany and is pending at a site in Cologne. The protocol will initially test BNT351 in people without HIV (delivered either subcutaneously or intravenously), followed by administration to a cohort of people living with HIV if safety is established.

Researchers affiliated with the EU2Cure Consortium have registered a new clinical trial that plans to investigate combinations of candidate latency-reversing agents at several sites in the Netherlands. Named PLUTO, the drugs under assessment are pyrimethamine, lenalidomide, and topiramate. Several dual combinations will be tested: pyrimethamine + lenalidomide, pyrimethamine + topiramate, and lenalidomide + topiramate. Results from a prior study of pyrimethamine were published in the journal Science Advances in 2023. Additional background on this work can be found in the excellent meeting report from the European AIDS Treatment Group (EATG): STEPS11: A Community Initiative to Design the Pathway to a Durable ART-Free Control of HIV Infection (see page 6), which is dedicated to the memory of our dearly missed activist colleague Giulio Maria Corbelli.

The ACTG is planning a small phase I study of the tyrosine kinase inhibitor dasatinib to assess safety and any effects on the size of the intact HIV reservoir in people on antiretroviral therapy (ART). Dasatinib has been reported to have potential anti-reservoir activity in laboratory studies, but results from a low-dose study in Spain with 60 participants were presented at CROI this week (abstract #385) and no significant effects were documented after 24 weeks of follow up. Five participants in the Spanish study discontinued due to side effects including headache, facial edema, and dyspepsia/diarrhea. The ACTG protocol involves a slightly higher dose (100mg vs 70 mg daily), and the researchers will surely review the new results presented at CROI before proceeding.

Updates to Enrollment Status

Based on information contained in the EATG report mentioned above, stating that results are anticipated this year, the status of the ORBIT trial in the Netherlands evaluating panobinostat, lenalidomide, and pyrimethamine as candidate latency-reversing agents has been changed to open for enrollment despite the registry entry is showing “unknown status.” The principal investigator Casper Rokx has since kindly shared an update that the study is now completed with analysis underway, so the listing will revised accordingly this next month.

We’ve also received information that the large ACTG A5417 trial of dual bNAbs taking place in Botswana and South Africa is now closed to enrollment, with 145 participants enrolled. The protocol is investigating whether receipt of the long-acting bNAbs 3BNC117-LS and 10-1074-LS can promote enhanced control of HIV viral load after an analytical treatment interruption (ATI).

Six studies in the listing are now completed and have been shifted to table 3:

• A trial sponsored by Gilead Sciences of a bispecific T cell engager now saddled with the name amtabafusp (formerly known as GS-8588). Preliminary safety data were presented during a poster session at CROI 2026 (abstract #371), with a high rate of mostly mild/moderate adverse events reported including reversible dermatologic issues in 24 out of 54 participants (44%). The abstract concludes: “Forthcoming immune activation and reservoir data will further elucidate the mechanism of action of ABF and the risk/benefit profile of BsTCEs for HIV cure.”
• SynactHIV, a small French ANRS protocol testing the latency-reversing activity of the drugs decitabine and romidepsin. To the best of our knowledge results are pending, but some perspectives from participants are included in the EATG STEPS11 meeting report based on a presentation by Christel Protièr (see page 9).
• The Merck-sponsored assessment of interactions between their TACK candidate MK-4646 and the TB drug and liver enzyme inducer rifabutin that recruited HIV-negative participants in Wisconsin.
• A phase I/II evaluation of IMC-M113V, an intervention called a T-cell receptor-based bispecific that can recruit T cells into responding against HIV-infected cells even if the natural receptor on the T cell doesn’t recognize the virus (e.g. allowing T cells specific for the flu or CMV to recognize and potentially eliminate HIV-infected cells). Results from the initial phase I safety and pharmacokinetics portion of the study were just published in Nature Communications (see below).
• Gilead Sciences phase Ib trial of two therapeutic vaccine candidates, GS-1966 and GS-1144. GS-1966 is based on a chimpanzee adenovirus vector while GS-1144 is a self-amplifying mRNA-lipid nanoparticle. A preliminary report on the induction of T cell responses against HIV among participants was presented at CROI last year.
• A study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) investigating therapeutic vaccination with a three-pronged (trimer) form of the HIV Envelope protein, designed to promote induction of broadly neutralizing antibodies. Results are pending.

New Links to Study Results

An analysis from the SCOPE ATI study describing the impact of participants’ natural neutralizing antibody responses (called autologous neutralizing antibodies or aNAbs) on HIV viral load rebound has been published in preprint form on the bioRxiv server. The paper reports that the activity and targeting of aNAbs influences which HIV variants are able to emerge from the reservoir during treatment interruption. More extensive results from the trial were presented at CROI 2026, and links to that abstract will be added when it becomes publicly available (hopefully next month). The new data provides an unprecedented look at biomarkers associated with viral load rebound during ATI, thanks to the commitment of participants and study staff – including the amazing Becky Hoh at San Francisco General Hospital – to scheduling study visits three times a week during this period. Some biomarkers showed changes a month before viral load became detectable in the blood, and notable differences were observed based on the degree of viral load control participants displayed prior to ART initiation.

Two medRxiv preprints were published in early February related to the RIO trial of dual bNAbs in early-treated people with HIV in the UK and Denmark. A submission dated February 4 reports on the primary results presented at CROI 2025 by Dr. Sarah Fidler (see blog post from May of last year and reporting by Simon Collins for HIV i-Base). Another paper posted the day before describes associations between T cell responses targeting HIV and the extended control of viral load during ATI observed among many bNAb recipients. The trial now has an additional arm C, with additional sites in Germany, Spain, Netherlands, and Sweden.

As noted in the section above, results from the phase I portion of a clinical trial of a T-cell receptor-based bispecific named IMC-M113V were published in Nature Communications on January 31. Results from the second phase, which included an ATI, were presented by Beatriz Mothe at CROI 2025, describing potential anti-reservoir effects and modulation of viral load rebound.

The TATELO study tested whether dual bNAbs could sustain control of HIV during an ATI in children with HIV in Botswana. Primary results were published in 2023. A new analysis in the Journal of Clinical Investigation looks at correlates of viral load suppression during ATI, finding that different types of natural killer (NK) cell responses were linked to faster rebound (NK cells expressing a marker called KIR2DL1) and delayed rebound and lower HIV reservoir size (NK cells expressing the NKG2A marker). A genetic signature among human leukocyte antigen (HLA) genes was also associated with delayed rebound and lower HIV reservoir size. Conversely, T cell responses did not show associations, suggesting NK cells are playing an important role in this setting. The TATELO Plus study is now underway in Botswana evaluating a triple bNAb combination using a similar design.

In the journal Nature Medicine, researchers present a detailed assessment of responses to anti-PD-1 therapy in people with cancer and HIV that were associated with HIV reservoir declines. The data derive from a multisite study sponsored by the National Cancer Institute and the journal has made the paper open access. The abstract summary states: “these findings define immune pathways that help identify PLWH most likely to experience reservoir decay with anti-PD-1 therapy and suggest that sustained ISG [interferon-stimulated gene] activation may contribute to reservoir reduction and prevention of viral rebound upon ART interruption.” Unfortunately, prospects for the use of PD-1 inhibition outside of the cancer setting remain uncertain; a large clinical trial in healthy people on ART was reported at CROI 2026 (see Liz Highleyman’s coverage for Aidsmap) and there were a number of notable immune-mediated side effects. The proportion of participants experiencing viral load control in this trial was considered insufficient to justify further development by the sponsor, AbbVie.

To the credit of the researchers involved and the openness of the participants, multiple social science studies are being published describing the experiences of the young South African women (members of the FRESH cohort) who participated in the first interventional ATI trial on the continent. In the Journal of the International Association of Providers of AIDS Care (JIAPAC), Ali Ahmed and colleagues report on stress and coping among 19 of the 20 participants; the paper is open access and includes an excellent plain language summary of the findings immediately after the abstract.

AGT103-T, a gene therapy approach that modifies CD4 T cells to resist HIV and then reinfuses them, showed a relatively limited capacity to lower viral load during ATI in an initial trial. An investigation of effects on the size of the intact HIV reservoir was published in the journal AIDS in mid-February, reporting that in six evaluable participants levels eventually fell below the detection limit of the test. The findings are considered exploratory, but the authors conclude “they offer a compelling rationale for advancing AGT103-T into larger, more mechanistic studies designed to capture early post-infusion dynamics and accelerate progress toward a functional cure for HIV.”

Another recent publication in the journal AIDS reports on a novel metric of ART penetration into the cerebrospinal fluid (CSF), based on samples from the ACTG A5321 observational HIV reservoir study. The analysis found that higher levels on the metric were associated with undetectable HIV DNA in CSF and better cognitive function.

A link was added to the abstracts from the 2025 European AIDS Clinical Society (EACS) conference for the Spanish clinical trial of low dose dasatinib mentioned in the opening section above (the BCN04-Dasa trial). Abstract PS07.3 at the conference reported on a laboratory investigation of NK cell responses involving samples from just six participants, indicating an enhancement of the capacity of NK cells to kill HIV-infected cells. These in vitro  effects do not appear to have translated to measurable anti-reservoir activity in the overall study population (see abstract #385, CROI 2026).

Results from the ANRS-sponsored DOLUVOIR observational study are described in the journal Communications Medicine. The research obtained samples from multiple anatomic sites and found that ongoing HIV transcriptional activity (the generation of HIV RNA from HIV DNA, which doesn’t necessarily equate to full viral replication) wasn’t associated with the development of resistance to dolutegravir. The authors state: “Our results suggest that the detectable transcriptional activity stems predominantly from defective proviral DNA.”

Seemingly in contrast, results from a trial that doubled the dosage of dolutegravir in people with HIV on ART have now been peer reviewed and published in the open access journal Elife (a preprint of these findings was briefly covered in last month’s blog post). The authors present a case that the increased dosage reduced markers of HIV persistence in a way that suggests viral replication was ongoing, despite a large volume of prior literature indicating that ART is typically fully suppressive and prevents ongoing replication and viral evolution. One of the paper’s co-authors, Courtney Fletcher, is among a cadre of researchers who’ve long argued – in the face of diminishing evidentiary support – that ART is likely not fully suppressive. The study is small and too technical for me to be able to offer an opinion, but further data is certainly needed to support the argument being made. Both the reviewer comments and author responses are available, and may be illuminating. One reviewer concludes:

“The abstract and results are only marginally different than the original version and still read as definitive when the evidence is only hypothesis generating. For these reasons, the level of evidence remains incomplete as before.”

Another study of the effects of increased ART dosing on the HIV reservoir is now ongoing in Spain, and may help shed light on the veracity of these reported results.

The last newly added link this month is not to results, but rather a published description of an ongoing protocol at Emory University designed to evaluate whether the drug baricitinib can reduce HIV levels in the central nervous system.

There were 14 updates to the TAG listing for December 2025, and a further eight for January 2026. No new HIV cure-related studies were identified in registries during this period.

Updates to Enrollment Status

A clinical trial testing the Janus kinase inhibitor baricitinib in Barcelona that was added to the listing in July 2025 is now open for enrollment. The study will evaluate baricitinib’s safety, tolerability, and effects on CD4 T cells, with secondary endpoints including measurements of the HIV reservoir.

Four studies have closed to enrollment:

• A protocol investigating drug interactions between Merck’s candidate TACK molecule MK-4646 and the TB drug (and liver enzyme inducer) rifabutin, which recruited HIV-negative participants.
• An observational study evaluating two candidate biomarkers that may be associated with HIV DNA levels in people with HIV on antiretroviral therapy (ART).
• A trial at the National Institutes of Health (NIH) Clinical Center and Rockefeller University investigating dual broadly neutralizing antibodies (bNAbs) in people on antiretroviral therapy (ART). The protocol enrolled 105 people and administered the long-acting bNAbs 3BNC117-LS and 10-1074-LS. Participants are now being offered the opportunity to join a follow up study involving an analytical treatment interruption (ATI).
• The suspension of a study of an HIV vaccine construct in people with HIV has been lifted, but the protocol is now in follow up and closed to further enrollment. The focus of the research is assessing the potential to promote the development of bNAbs using a protein named 426c.Mod.Core-C4b (delivered with an adjuvant).

An investigation of immunization with an HIV envelope protein, CH505 TF chTrimer, is now listed as temporarily paused but no reason is given in the registry entry.

One trial has been completed and moved to table 3: an assessment of whether people with a specific genetic profile who started ART early have an increased potential to achieve posttreatment control of HIV viral load after an ATI. Results are likely to be presented at either CROI or the AIDS 2026 conference in July.

New Links to Study Results

Data from several of the studies in the listing provided the basis for two papers and an accompanying commentary published in the journal Nature on December 1^st, World AIDS Day. The reported analyses focus on immunological parameters associated with achieving post-intervention control (PIC) of HIV viral load after an ATI.

Zahra Kiani and colleagues assessed data from 12 participants in four clinical protocols testing candidate therapeutic interventions (primarily bNAbs) that included an ATI (MCA-906, MCA-965, TITAN and eCLEAR). The research identified multiple properties of participant HIV-specific CD8 T cells that were linked to an increased likelihood of controlling viral load after ART interruption, including: baseline proliferative capacity (ability to copy themselves), cellular youthfulness referred to as stemness, and capacity to kill cells displaying HIV fragments in a lab dish (cytotoxicity). The administration of bNAbs was associated with an increase in HIV-specific CD8 T cell stemness, which in turn was related to superior CD8 T cell metabolic fitness, reduced markers of T cell exhaustion, and a greater chance of post-intervention viral load control.

In a separate paper, Michael Peluso and colleagues from the University of California San Francisco report broadly similar findings from a small, amfAR-funded multi-intervention trial in which the majority of the participants displayed some degree of control viral load after ATI (including some cases of persistently undetectable levels). Factors associated with post-intervention control included robust CD8 T cell expansion (proliferation) in response to HIV viral load rebound and CD8 T cell expression of TCF-1, a marker of cellular stemness.

In an accompanying commentary, Jonathan Li states:

“The two studies offer a coherent vision for how ART-free HIV remission might one day be achieved. They underscore three key principles. First, the quality of anti-HIV CD8+ T cells matters, especially the presence of stem- cell-like antiviral CD8+ T cells that are capable of sustained proliferation and cytotoxic responses. Second, bNAbs and T cells might act in synergy, given that effective anti-HIV antibodies can delay or reduce the immediate post-ART viral rebound (or do both) and create an immune environment that is conducive to enhancing effective cellular responses. Third, therapeutic combination approaches that incorporate several branches of the immune response are likely to hold the greatest promise.”

Links to another eleven new publications were also added during this period:

In the journal Communications Medicine, Lucia Bailón and colleagues in Spain report that the magnitude of HIV-specific T cell responses at the time of ATI were associated with a greater chance of remaining off ART for a 12-week interruption in trials of a therapeutic vaccine either alone or combined with the TLR7 agonist vesatolimod. The criteria for ART restart in these studies was a single viral load >100,000 copies/ml or >10,000 copies/ml for eight consecutive weeks, meaning that only a relatively minor degree of viral load control was required to stay off ART for the duration of the 12-week ATI.

A preprint (not yet peer reviewed) article on the ongoing RIO trial in the UK is available on the medRxiv server. Marcilio Fumagalli and colleagues report that receipt of dual bNAbs was associated with an accelerated decrease in the size of the intact HIV reservoir. Susceptibility of viruses in the reservoir to the bNAb 10-1074 and participants’ natural (autologous) antibody responses was significantly correlated with time to viral load rebound after ATI. Rebounding HIV showed evidence of the development of resistance to the bNAb 3BNC117 but not 10-1074; the likely explanation is that the parts of HIV targeted by different bNAbs can have differing capacities to mutate (similar to how HIV develops resistance more easily to some antiretroviral drugs compared to others).

Three new papers were published over the holiday period describing results from social science studies involving young women participating in an ATI protocol in the FRESH cohort in South Africa:

• In the journal HIV Research and Clinical Practice, Karine Dubé and colleagues assessed issues related to potential risks of sexual ATI transmission during ATI, revealing the challenges that this can raise for participants. Table 3 in the open access article offers recommendations for improving the promotion of protective behaviors during ATI trials.
• Krista Dong and colleagues in Frontiers in Public Health report on a socio-behavioral study involving five male partners and five members of the families of ATI trial participants.
• Ali Ahmed and colleagues investigated the psychological impact of participating in the trial and their findings were posted online in AIDS Research and Human Retroviruses on December 22nd. The ATI was considered generally well tolerated, with anxiety only transiently increasing pre-ATI, but for the subset of participants who achieved extended posttreatment control of HIV viral load the prolonged time off ART was associated with a persistent elevation of anxiety and depression. The authors note that this latter finding was “possibly because worries about viral rebound and HIV transmission persisted.” Similar concerns have previously been reported by Luis Canales, a posttreatment controller in a US-based study .

The cytokine interleukin-2 (IL-2) was the first intervention suggested to have the capacity to potentially reverse HIV latency and flush out the viral reservoir, back in the late 1990s. However, studies involving ART interruption didn’t demonstrate notable effects on HIV viral load rebound. Results from a recent trial in people on ART conducted at Case Western Reserve University have been published in Scientific Advances, reinforcing that IL-2 can stimulate HIV production by latently infected CD4 T cells but with side effects that caused the protocol to be stopped early. In the discussion section of the paper, the authors cite the development of potentially safer IL-2 variants that they argue may deserve evaluation in the context of HIV cure research.

A preprint article on a trial testing a doubled dose of the integrase inhibitor dolutegravir has been posted by medRxiv. The authors outline evidence that the increased dose led to reductions in measures of the HIV reservoir and immune activation, suggesting the participants’ previous regimens weren’t fully blocking HIV replication. The results run counter to a considerable amount of prior evidence that standard ART typically fully suppresses HIV, and it may be prudent to wait for the peer reviewed version before considering the possible implications.

Finally, four newly linked papers focus on gut-related aspects of HIV cure research:

• A preprint on the bioRxiv server presents evidence that gut microbiome diversity influences the response to N-803, a souped-up version of the cytokine IL-15. The analyses derives from a trial conducted at the University of Minnesota.
• Canadian researchers assessed the recovery of γδ (gamma-delta) T cell levels in the gut in people on ART, based on samples taken at the baseline visit for a trial testing vedolizumab (an FDA approved antibody that targets the α4β7 integrin receptor on cells).
• An Italian study investigated the effects of three months of ART initiated during primary HIV infection on various gut abnormalities, finding that the treatment didn’t fully correct HIV-mediated damage (the paper is published in Pathogens & Immunity).
• A paper detailing a protocol designed to test the effects of fecal microbiota transplantation on immune activation in people with HIV has been made available by the journal Trials. Sponsored by the Pan-Canadian Network for HIV and STBBI Clinical Trials Research, the study is now completed with results pending.

There were 10 changes to the TAG listing in the November update. The completed studies table has also been slightly reorganized to separate the previous “antibodies” category into more specific groupings: anti-α4β7 integrin antibodies, broadly neutralizing antibodies, and intravenous immune globulin (IVIG).

New Additions

Only one new HIV cure-related trial was added since the previous update: an evaluation of interactions between Merck’s MK-4646 and the TB drug (and liver enzyme inducer) rifabutin in 18 HIV-negative participants. The study is due to be completed by the end of the year. MK-4646 is an experimental candidate in a new class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) specifically designed to promote the destruction of HIV-infected cells (categorized as Targeted Activator of Cell Kill or TACK molecules, see prior blog coverage for details). A trial of MK-4646 in people with HIV is ongoing in Moldova and Romania.

Thanks to a poster on Bluesky for alerting us to this study, which wasn’t registered as HIV-related and hence was missed when first posted in clinicaltrials.gov at the end of September.

Updates to Enrollment Status

Four trials have been moved to the completed studies table, along with the addition of a past observational protocol relevant to HIV cure research that was previously missing from our listing (the completed CHRONOS study in Australia).

In three instances, the reason for the move is lack of updates to registry records suggesting the trials are no longer ongoing (in one case, it’s unclear if the protocol ever started). Attempts to ascertain status via emails have been unsuccessful:

• A vedolizumab (anti-α₄β₇ integrin antibody) study at the Ottawa Hospital Research Institute in Canada for which results were presented at CROI in 2019.
• An investigation of the functional cure potential of UB-421 (an antibody inhibitor of HIV binding to CD4 receptors), which was due to be completed in June 2025 but has never been listed as open for enrollment.
• A trial evaluating the anti-HIV reservoir activity of the immunomodulators lenalidomide and adenosylmethionine at the First Affiliated Hospital of Zhejiang University in China, now showing “unknown status” with an estimated completion date of November 2024.

The fourth addition is a therapeutic HIV vaccine trial sponsored by Hookipa Biotech testing arenavírus vectors, which is now listed as “terminated: business decision.”

New Links to Study Results

Since the last update in October, scientific papers have been published related to several studies in the listing:

An article describing the design of AbbVie’s large phase 2 trial of the PD-1 inhibitor budigalimab and the α₄β₇ integrin inhibitor trosunilimab was made available online by the journal Contemporary Clinical Trials on November 9th. The open access paper focuses particularly on how the researchers approached the analytical treatment interruption (ATI) included in the protocol, including drawing on “consensus recommendations, existing interventional studies with ATI, engagement with HIV experts and HIV community members, correspondence with regulatory agencies, phase 1 study results, and the experience of PWH.”

The authors note that the study is unique in international breadth, involving 90 sites across 12 countries. With 160 participants, it’s also the largest HIV cure-related trial including an ATI conducted to date. However, since the registry entry was initially updated at the end of September to “completed,” the record has been amended again to state: “Terminated Company Decision.” No reason is given but it may be cause to temper hopes regarding the results, which are expected to be presented at CROI 2026.

Two new papers describe analyses involving 2000HIV cohort study participants in the Netherlands. In EBioMedicine, researchers report on differences in markers of gene activity between people who naturally control HIV viral load and non-controllers. A study published in Frontiers in Immunology also analyzes spontaneous HIV controllers in the cohort, comparing those who maintain low viral loads with elite controllers who are able to suppress HIV replication to undetectable levels. The study explores a wide range of immunological parameters and identifies commonalities and differences between the groups that  may be important for HIV cure research.

Investigators conducting the Last Gift study have published an analysis of potential links between HIV reservoir measures and gut microbiota across five different segments of the gastrointestinal tract. A number of associations were identified that varied by location, but the work is exploratory and statistical significance wasn’t achieved when the results were adjusted for multiple comparisons. The authors note that the possibility of varying interactions along the GI tract should be considered when attempting to design microbiota-based strategies for modulating the HIV reservoir.

The CHRONOS observational study ran from 2015-2018 and initially published findings related to the effect of the circadian rhythm on HIV RNA expression in the Journal of Infectious Diseases in 2021. In a newly published paper in the Journal of Virus Eradication, Jared Stern and colleagues report evidence that acute stress can induce the transcription of HIV RNA by reservoir cells containing HIV DNA. There was no indication of changes in the size of the HIV reservoir.

For October 2025, there were 29 updates to the TAG listing. We’re very grateful to the employees at the National Center for Biotechnology Information who are continuing to maintain the trial registry clinicaltrials.gov and scientific literature database PubMed during the current US Federal government shutdown (likely without pay).

New Additions

Three newly registered HIV cure-related clinical trials were added:

The DART DELIVER-02 study is evaluating two antibody-based constructs called dual affinity retargeting (DART) molecules. The DART molecules are designed to bind the CD3 molecule expressed on all T cells, in tandem with the HIV envelope protein when it’s expressed on the surface of virus-infected cells. The aim is to endow any T cell with the capacity to recognize and destroy cells containing HIV. The candidates being tested in the study (MGD014 and MGD020) are manufactured by the biotechnology company Macrogenics, with each designed to recognize different parts of the HIV envelope. Both MGD014 and MGD020 have previously been tested in people with HIV, with no apparent safety issues. The new protocol involves a brief antiretroviral therapy (ART) interruption and some participants will also receive the HDAC inhibitor vorinostat. Recruitment has begun at a University of North Carolina site, with additional locations in Kenya listed in the registry entry but not yet open for enrollment.

The ACTG network is initiating a small trial of the aminobisphosphonate drug alendronate in people with HIV. Better known by the trade name Fosamax, alendronate is an approved treatment for osteoporosis and bone disease that has been reported to potentially exert HIV latency reversal activity. The study aims to assess any effects of alendronate on the size and activity of the HIV reservoir.

Emory University is launching a second trial of the Janus kinase inhibitor baricitinib in people with HIV on ART (an ongoing protocol at the institution is focused on central nervous system effects of the drug). The design of the new study includes an analytical treatment interruption (ATI) to investigate whether receipt of baricitinib can maintain HIV suppression in the absence of ART.

Two long-running observational studies were also added to table 2 in the TAG listing, because samples from participants are now being used to advance HIV cure research:

• The SCOPE cohort at the University of California, San Francisco.
• A leukapheresis sampling protocol at the National Institutes of Health (NIH) Clinical Center in Bethesda, which collects plasma and lymphocytes for use in studies.

Updates to Enrollment Status

Three trials have opened for enrollment since September:

• The AbVax study in the UK testing broadly neutralizing antibodies (bNAbs) and vaccines designed to induce T cell responses against HIV.
• A multi-intervention protocol sponsored by the US Military HIV Research Program (MHRP), which will administer two bNAbs and three different vaccine vectors to people who began ART during acute HIV infection.
• An investigation of the effects of intensifying ART with lenacapavir, based on evidence that the capsid inhibitor may also have the capacity to promote innate antiviral immune responses.

The release of NIH funding has allowed the ACTG to lift a pause and restart enrollment in several HIV cure-related protocols involving administration of bNAbs and HIV vaccines: NCT06205602, NCT05719441 and NCT06071767.

Three additions were made to the completed studies table:

• Abbvie’s large phase 2 investigation of the PD-1 inhibitor budigalimab and the α₄β₇ integrin inhibitor trosunilimab has now concluded. Results may be available for presentation at CROI 2026.
• A trial in Spain that evaluated the tyrosine kinase inhibitor datanasib. To our knowledge results are pending.
• A trial of intensifying ART with efavirenz conducted at the Washington University School of Medicine in St. Louis that wasn’t previously included in our listing – it was only added to the clinicaltrials.gov registry last month, but was completed in December 2024.

New Links to Study Results

Findings from the first iteration of the IMPAACT P1115 pediatric HIV cure research study were published in the Lancet HIV in September. Four cases of extended ART-free remission were documented after an ATI, with one of the children experiencing a late HIV viral load rebound after about 1.5 years off ART. The results were first presented by Dr. Deborah Persaud at CROI 2024 (see webcast and coverage by Liz Highleyman for AIDSMap).

Phase 1 trial results for AbbVie’s PD-1 inhibitor are now available in Nature Medicine, following their presentation by Jean-Pierre Routy at the 2023 European AIDS Conference. The paper reports evidence of enhanced control of HIV viral load after an ATI, but the pending findings from the 163-person phase 2 study will provide a clearer answer as to whether the approach holds promise.

Two links were added for the Tatelo Study that tested dual bNAbs as a potential ART alternative in children in Botswana. In Clinical Infectious Diseases, the researchers describe the long-term outcomes among participants who underwent an ATI, uncovering no evidence of any negative consequences. A link was also added to an AIDS 2024 abstract previously missed, which reports possible improvements in growth associated with bNAb-mediated HIV suppression (this analysis is as yet unpublished). The primary results from the trial were published in the journal Science Translational Medicine in 2023, and a further assessment of the approach using three different bNAbs is now underway (the Tatelo Plus Study).

Researchers in the Netherlands published results derived from their very large 2000HIV cohort study and a substudy on innate immunity in the open access journal EBioMedicine. The analyses focus on the profile of natural killer (NK) cell responses in study participants controlling HIV viral load in the absence of ART.  

An investigation of the comparability of different approaches to measuring the HIV reservoir, reported in the journal AIDS, drew samples from participants in two protocols in the listing: a completed short-term ATI study and an ongoing observational leukapheresis sampling project, both at the NIH Clinical Center in Bethesda.

Results from a 60-person trial of Bacillus Calmette-Guérin (BCG) vaccination conducted in Zurich were published in Open Forum Infectious Diseases. The purpose was to evaluate safety and any effects on the HIV reservoir (while BCG is primarily known as a partially effective TB vaccine, it has also been shown to modulate innate immunity). The researchers report no serious adverse events, but no detectable alteration in intact HIV reservoir size. Typical BCG local skin reactions and scarring were common.

Samples from participants in the ACTG network A5321 cohort study were included in an analysis of how levels of intact and defective HIV change in response to ART, published in Open Forum Infectious Diseases.

The listing entry for the Netherlands Cohort Study on Acute HIV infection (NOVA) saw three new links added. The first is to a poster abstract (eP004) presented at the recent 2025 European AIDS Conference, which describes evidence of proliferative HIV-specific CD8 T cell responses driving virus escape mutations and potentially also promoting viral integration into inhospitable regions of infected CD4 cell genomes that are less likely to allow for HIV to reemerge. In a separate paper in the Journal of Virus Eradication, social scientists report on the perceptions of HIV cure research among 20 cohort members. During in-depth interviews, participants noted limited knowledge of the cure research field. Half were open to participating in studies with short-term ATIs, but only one was open to the idea of extended ATIs with concerns about viral load rebound and risk of onward transmission prominent among the respondents. The third NOVA addition is a link to a historical paper from 2020 in BMJ Open providing background on the study cohort.

Another link to the abstracts from the 2025 European AIDS Conference was added for the APRIL observational study in France. The abstract (PS07.2) outlines a laboratory analysis of the effects of lenacapavir on the HIV reservoir using participant samples, providing additional evidence that the drug may be capable of enhancing both innate and adaptive immune responses by degrading the integrity of the HIV capsid and essentially rendering viral components more visible.

Lastly, a link was added to the clinicaltrials.gov results page for a completed study of the DART molecules MGD014 and MGD020. The detailed presentation of participant data in the registry entry format makes interpretation difficult, but it appears that the interventions were safe which has allowed for the initiation of the DELIVER 02 trial mentioned at the beginning of this post.