The June 2025 update to TAG’s listing features 11 changes.
New Additions
Two studies were added:
The ACTG has registered a new trial of dual broadly neutralizing antibodies (bNAbs), VRC07-523LS and PGT121.414.LS, in people who initiated antiretroviral therapy (ART) during acute HIV infection. The protocol includes an analytical treatment interruption (ATI) to assess whether receipt of the bNAbs is associated with continued suppression of viral load after ART withdrawal. The study isn’t yet recruiting and may be affected by the withholding of National Institutes of Health (NIH) funding for the ACTG by the current US administration. The registry entry lists sites in Brazil and Peru, so plans for the study could also be affected by the current “pause” on provision of NIH grant subawards that fund international clinical trial units.
Researchers at the Assistance Publique – Hôpitaux de Paris in France are launching a new observational study investigating contributors to the persistence of low level HIV viral load that occurs in a subset of people on ART. Enrollment is pending.
Updates to Enrollment Status
A phase I ACTG study of a vaccine intended to promote the development of neutralizing antibody responses against HIV is now listed as open for enrollment. The vaccine consists of a stabilized form of the HIV envelope protein in a natural trimer (three-pronged) structure. The protocol is recruiting adults with HIV on ART with suppressed viral loads at multiples sites in the US.
A trial sponsored by ViiV Healthcare investigating a bispecific bNAb (capable of recognizing two different targets on HIV’s outer envelope) has reopened for enrollment after briefly being listed as closed. The pause may have been related to the stepwise protocol design which involves multiple sequential cohorts, some initially receiving single doses before multiple doses are evaluated.
Two entries in the listing have now closed to enrollment and are in follow up:
- AlloReSIST, which is testing an adoptive immunotherapy approach involving infusions of HIV-specific T cells in people who’ve received a stem cell transplant.
- A study being conducted by the IMPAACT Network monitoring treatment outcomes in children who received early ART to potentially identify candidates for participation future HIV cure-related protocols.
There are three additions to the completed studies table (table 3).
A trial that recruited people who acquired HIV during the Antibody-Mediated Prevention (AMP) study at sites on the African continent. Investigators assessed whether receipt of the bNAb VRC01 prior to HIV acquisition enhanced the potential to control HIV viral load after an ATI. All participants had initiated ART rapidly after HIV diagnosis. Results were published recently in the Journal of the International AIDS Society, reporting some cases of post-treatment viral load suppression but with no evident impact of prior receipt of VRC01.
A completed trial in Belgium was identified from the European clinical trials registry: a first-in-human assessment of new type of non-nucleoside reverse transcriptase inhibitor (NNRTI) called a Targeted Activator of Cell Kill (TACK) molecule. These molecules have the potential to not just inhibit HIV replication but also trigger the death of virus-infected cells. The approach is being developed by Merck who’ve reported promising laboratory results. The outcomes from this completed trial of an initial candidate codenamed MK-4646 haven’t been publicly presented to our knowledge.
A study of a dendritic cell-based therapeutic vaccine registered to take place in Brazil has been moved to the completed table because the clinicaltrials.gov record hasn’t been updated for some time, and the listed contact hasn’t answered email requests for information on the status of the study. It’s not known if the trial ever took place.
New Links to Study Results
Links were added to new papers reporting results from two of the trials in the listing:
- A phase I evaluation of an adoptive immunotherapy strategy involving infusions of HIV-specific T cells, published in Nature Communications. The data were previously described in conference abstracts, indicating that the intervention was safe with some hints of activity against the HIV reservoir.
- A small phase I trial of N-803, a modified version of the cytokine IL-15, published in JCI Insight. The investigators found some evidence of a reduction in the number of cells containing HIV RNA or DNA in lymph nodes of six participants with available samples, but the decline didn’t reach statistical significance. These reductions were associated with markers of natural killer (NK) cell activity, suggesting N-803 enhanced NK cell function. In terms of safety, there were similar grade 3 injection site reactions to prior studies including reddening of the skin and induration. There were also some cases of transient low estimated glomerular filtration rate (eGFR). Additional studies of N-803 in people with HIV are ongoing (see table 1 in the listing).
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