For August 2025, there were eight updates to the TAG listing.
New Additions
A study sponsored by the ANRS RHIVIERA project in France plans to investigate the JAK1/JAK2 Inhibitor baricitinib and the mTOR Inhibitor sirolimus in people who started antiretroviral therapy (ART) soon after HIV acquisition. Baricitinib is also being tested in several other ongoing studies, spurred by laboratory evidence of potential activity against the HIV reservoir. Sirolimus has been reported to reduce HIV DNA levels in a prior ACTG-sponsored trial.
The protocol design involves four arms in which participants will receive baricitinib, sirolimus, baricitinib plus sirolimus, or placebos once daily for ten weeks. Participants receiving just one of the drugs will receive a placebo of the other, to ensure assignments are blinded. An analytical treatment interruption (ATI) will be initiated two weeks into the dosing period, meaning that participants will receive the medications (and/or placebos) for eight weeks while off ART unless restart criteria are met. The primary endpoint is time to viral load rebound of sufficient magnitude to trigger ART restart, but information on the exact viral load criteria isn’t provided in the registry entry.
Updates to Enrollment Status
A phase I trial in Moldova and Romania assessing Merck’s TACK molecule candidate MK-4646 wasn’t open at the time it was added to the listing last month, but has since begun recruiting. The same is true for ViiV Healthcare’s investigation of the combination of a long-acting broadly neutralizing antibody (bNAb) N6-LS and the CD4 attachment inhibitor fostemsavir, which is now enrolling at sites in Florida and Missouri in the US.
IAVI have officially announced that enrollment has begun for their C114 protocol assessing a vaccine that uses a Gorilla adenovirus vector to deliver components derived from HIV designed to induce virus-specific T cell responses. The trial will include both people with HIV and an HIV-negative cohort, with sites located in South Africa and Zimbabwe.
A study of a Gilead Sciences bispecific T cell engager candidate, GS-8588, is now listed as closed to further enrollment on the University of Pennsylvania website. As is often the case with Gilead Sciences, the phase I study hasn’t been registered in clinicaltrials.gov (registration of phase I trials isn’t mandatory under the relevant regulations).
A PENTA Foundation sponsored trial of therapeutic vaccination in children and youth with HIV, titled HVRRICANE, has been completed (and moved to the completed studies table). Preliminary safety results were presented at CROI 2024, and increases in HIV-specific immunity were described in a poster at CROI 2025.
New Links to Study Results
Results from a combination HIV cure trial in Brazil that was completed in 2020 were published in the Journal of Infectious Diseases on August 14th. In TAG’s recently posted 2025 Research Toward a Cure and Immune-Based Therapies Pipeline Report, we noted that full results from this study hadn’t yet been formally disclosed, which was true at the time of going to press but unfortunately very quickly out of date. Thanks to co-author Andrea Savarino for letting us know about the publication.
The trial randomly assigned 30 participants into six small groups of five, receiving either:
- ART alone
- ART intensified with the addition of maraviroc (MVC) and dolutegravir (DTG)
- ART + MVC + DTG + nicotinamide (a form of vitamin B3 reported to have HIV latency-reversing potential)
- ART + MVC + DTG + auranofin (an antirheumatic drug reported to have potential anti-HIV reservoir activity)
- ART + DTG + dendritic cell-based therapeutic vaccine
- ART + DTG + nicotinamide + auranofin + dendritic cell-based therapeutic vaccine
Receipt of the interventions did not lead to any significant safety issues, and 26 of the 30 participants subsequently consented to undergo an ATI. Two participants who’d interrupted ART earlier during the study were excluded, and another two participants declined the ATI.
Analyses of ATI outcomes found statistical trends toward lower viral load setpoints in the multi-intervention group (group six), when compared to both their pre-ART baselines and participants in the other arms. Additionally, one participant experienced extended posttreatment control of viral load to undetectable levels for 78 weeks prior to rebound, and two additional participants maintained low viral loads for 22 weeks and then reinitiated ART. All three had received nicotinamide, but the numbers were too small to document a robust statistical association.
The authors are now planning a larger 70-person protocol in hopes of bolstering and validating their preliminary observations. In the new study, ten participants will serve as controls while 60 receive the same regimen as the multi-intervention group in the previous study, with maraviroc added during the first 44 weeks.
Notably, before the new publication, partial results from this study had been presented in several prior conference presentations and papers (see the links in the first entry in the “combinations” section of the completed studies table). The participant with the most extended period of posttreatment control was reported as a possible long-term remission case at the AIDS 2020 conference, and then posited at CROI 2021 to have potentially acquired a second HIV variant when they later experienced an HIV viral load rebound – this individual is described in the new paper, but the previous explanation offered for the return of viral load isn’t mentioned.
Several links were also added this month for results reported from the observational Last Gift cohort study. The project represents a novel and carefully considered approach to involving people with HIV reaching the end of life in HIV cure research. Participants consent to donate their bodies for rapid autopsy analyses after death, allowing for detailed investigations of HIV persistence and tissue distribution. The new links include papers in the journals AIDS Care, JAIDS, Life Science Alliance, and AIDS. Community advocates and social scientists are deeply involved in the work, and several have contributed to an article in the Journal of Infectious Diseases advocating for policy revisions to end discriminatory policies relating to anatomical donations from people with HIV and other infectious diseases.
Leave a Reply