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.
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