TAG HIV Basic Science, Vaccines, and Cure Project Blog

A delayed backgrounder on last month’s update to TAG’s listing. There were 13 changes for March 2026, including one newly registered clinical trial.

Notably, the last few weeks have seen some potentially encouraging signs for the future of funding support for HIV cure research from the National Institute of Allergy and Infectious Diseases (NIAID) at the US National Institutes of Health (NIH). On Monday April 6, the NIAID Council met and Acting Director Jeffery Taubenberger chose to highlight advances in understanding immune control of HIV in his public comments (the recording should soon be available on the NIH Videocast website). Later that day, the AIDS Research Advisory Committee met and approved a new notice of funding opportunity (NOFO) for the HIV clinical trial networks, including the ACTG which is conducting multiple HIV cure-related trials and contributes vitally to the field. TAG’s U.S. and Global Health Policy Director Elizabeth (Lizzy) Lovinger delivered comments at the meeting. It remains important to monitor whether these plans survive the multiple layers of review that the current US regime has imposed for proposed NIH funding.

New Additions

Researchers in Brazil are conducting a study of the effects of the drug spironolactone on the HIV reservoir. Spironolactone blocks certain cellular receptors and limits the effects of the hormones aldosterone and testosterone. Laboratory and humanized mouse studies have shown that the drug can suppress the transcription of HIV RNA by HIV DNA (a step required to generate HIV proteins) and may be able to contribute to “block and lock” approaches to stopping HIV reservoir activity.

Spironolactone is sometimes used as part of gender affirming care for transgender women because of its feminizing properties. This raises the possibility of studies in transgender women living with HIV who are already receiving the drug, but politically motivated bigotry-based restrictions on US funding support for studies involving transgender people are likely to close off this opportunity at the current time. Furthermore, the appalling widespread attacks on the humanity, dignity, and rights of transgender people will surely (and understandably) exacerbate distrust in research participation.

Updates to Enrollment Status

Seven studies in the listing had updates to enrollment status:

• The RIO trial of dual broadly neutralizing antibodies (bNAbs) has added a third arm (arm C) to investigate the role of multiple analytical treatment interruptions (ATIs) in promoting posttreatment control of viral load. This protocol amendment reportedly involves the addition of new study sites in Denmark, Germany, Spain, Netherlands and Sweden. According to the RIO website, arm C is already fully recruited so it’s unclear if all these sites were opened.
• A study of BNT351, a new bNAb being developed by BioNTech that was added to TAG’s listing last month, is now open and recruiting participants in Germany.
• Also now open for enrollment is an investigation of genetically modified chimeric antigen receptor (CAR) T cells in people with HIV at a site in Tianjin, China.
• The following trials have closed to enrollment:
  • NCT06652958, a study of the bispecific broadly neutralizing antibody VH4527079 sponsored by ViiV Healthcare.
  • NCT07028385, investigating the Janus kinase inhibitor baricitinib in people with HIV on antiretroviral therapy (ART) at a site in Barcelona, Spain.
  • NCT06240520, named the ORBIT study, assessing panobinostat, lenalidomide, and pyrimethamine as candidate latency-reversing agents. The researchers are aiming to have the results analyzed in time to submit for presentation at the Conference on Retroviruses and Opportunistic Infections (CROI) next year.
• One trial is now listed as completed and was moved to table 3: a phase I assessment of a DNA-based therapeutic HIV vaccine candidate named ICVAX, sponsored by Immuno Cure Holding (HK) Limited in Guangdong, China.

New Links to Study Results

Results from multiple studies in the listing were presented at the CROI 2026 conference in Denver, for which links will be added in the April update next week (during March, access to the abstracts remained restricted to conference registrants – they were made available to the public on April 8th).

Links to five new papers were added in March:

A report on a single dose study of the PD-1 inhibitor pembrolizumab conducted at the NIH Clinical Center, published in the Journal of Infectious Diseases. Although the intervention was safe and the abstract states that the results support the evaluation of multiple doses, there are now results available from multiple dose studies of a PD-1 inhibitor indicating that immune-related adverse events are a significant concern.

In the International Journal of Infectious Diseases, Anna Bershteyn and colleagues describe the capacity of a limiting antigen (LAg) test for antibodies against the HIV gp41 protein to detect viral load rebound in a study of a short-term ATI. Levels of the antibodies increased but, as anticipated, lagged behind the increase in viral load. The authors suggest the technology might have the potential to be adapted to provide low cost monitoring of viral load suppression in people on ART.

The ACTG A5345 protocol similarly investigated biomarkers of HIV viral load rebound during ATI. A paper in the Journal of Clinical Virology reports results from an analysis of antibody responses against HIV and describes findings similar to Bershteyn et al: antibody levels rose but lagged behind viral load. The authors conclude: “Although antibody levels did not predict viral rebound, tracking their longitudinal changes provided meaningful information about viral replication patterns and immune reactivation during and after rebound, offering a practical tool for monitoring ATI outcomes.”

Researchers at Radboud University Medical Center in the Netherlands have published new results from the 2000HIV cohort study in the open access journal iScience. The paper addresses factors contributing to persistent control of HIV in the absence of ART, finding that stronger innate immune responses and long-term reprogramming of innate immune cells (referred to as trained immunity) appear to play an important role. A particularly novel finding is that relatives of the HIV controllers showed similar innate immune profiles, while relatives of the people with HIV that lacked control of viral load did not.

An observational study sponsored by University Hospital in Strasbourg, France looked at the effects of dolutegravir-based regimens on the HIV reservoir and immune activation. Results reported in the journal Infectious Diseases Now demonstrate that the regimens reduced HIV DNA and immune activation in people who were previously treatment naïve or had detectable viral load because of the failure of a prior ART combination, but did not have measurable effects in people whose viral load was suppressed at the time of the switch.