The past month has seen few changes to TAG’s listing: since the previous update on June 15, two ongoing trials have closed to enrollment, one planned protocol has been withdrawn, and links have been added to three recently published papers presenting study results. For the second month in succession, no new HIV cure-related clinical studies have been registered in clinicaltrials.gov.
One of the studies that has closed to enrollment involves participants who acquired HIV during the Antibody Mediated Prevention (AMP) trial HVTN 704/HPTN 085, which enrolled men and transgender persons who have sex with men in the Americas and Switzerland. The follow up protocol (designated HVTN 804/HPTN 095), is evaluating whether the presence of the broadly neutralizing antibody (bNAb) VRC01 at the time of HIV acquisition altered the immune response to the virus to the extent that there’s a greater chance of control of viral load after an analytical treatment interruption (ATI). All the participants were started on ART soon after HIV diagnosis.
There were two separate AMP trials in different populations, and likewise there are two ATI studies enrolling AMP participants who acquired HIV and started ART – the other ATI protocol (HVTN 805/HPTN 093) remains open for participants in HVTN 703/HPTN 081, which enrolled cisgender women in several countries on the African continent.
Dr. Shelly Karuna from the HIV Vaccine Trials Network (HVTN) gave an excellent presentation about the two ATI studies for AMP participants at the 2023 Pre-CROI Community HIV Cure Research Workshop. After the workshop, Gail Broder from HVTN kindly made available the informed consent videos that were created for potential participants in this research:
- HVTN 804/HPTN 095 informed consent videos in English and Spanish.
- HVTN 805/HPTN 093 informed consent videos in English, Chichewa, Setswana, Shona, Sotho, Xhosa and Zulu.
The second study in the listing to have closed for enrollment during the last month is an AIDS Clinical Trials Group (ACTG) investigation of SAR441236, a trispecific (three-pronged) antibody designed to block three different targets on the HIV envelope. The antibody is made by Sanofi and combines the specificity of three previously described single bNAbs: VRC01, PGDM1400, and 10E8v4.
The protocol that’s been withdrawn was an ACTG trial that planned to assess the capacity of a dual bNAb combination, 3BNC117-LS and 10-1074-LS, to promote control of viral load after an ATI. The decision to not move ahead with the study was based on overlap with several other ongoing similar trials addressing the same question, including the RIO trial in the United Kingdom and RHIVIERA-02, which is due to get underway in France.
Added links to publications include a paper in Science Translational Medicine describing outcomes in a trial of a dual bNAb combination among HIV-positive infants in Botswana. The results have previously been presented at CROI, demonstrating that the combination was safely able to maintain HIV viral load suppression in a little under half the infants (44%) during an ART interruption.
In the Journal of Infectious Diseases, Javier Martinez-Picado and colleagues report additional results from a trial of obefazimod (formerly known as ABX464). Data from the study has been described previously in journal articles and at CROI 2020. Obefazimod has a novel mechanism of action that inhibits the generation of HIV RNA. The researchers report evidence of transient decreases in HIV DNA and levels of some inflammatory biomarkers. There were no serious adverse events but headache and GI side effects were common and three of the 24 HIV-positive study participants withdrew due to tolerability issues. The fate of obefazimod as a therapeutic candidate for HIV appears uncertain at the current time, because the manufacturer Abivax is now focused primarily on the use of the drug for inflammatory diseases and longer lists HIV in its research pipeline.
A publication by Karine Dubé and colleagues in the Journal of Virus Eradication reports results from a social science study investigating the perceived risks and benefits of enrolling in the Last Gift, a cure-related research project for people with HIV reaching the end of their lives. Participants join in order to contribute their bodies for postmortem autopsy studies of the HIV reservoir. The article outlines the significant community involvement in the development and oversight of the protocol, which has enrolled over 30 participants to date. Both participants and their next of kin/loved ones were interviewed, with overall findings indicating that perceived risks were minimal and the altruistic benefits of participation were valued by both groups.
Since last month’s update, the clinicaltrials.gov online registry that is the primary source for TAG’s cure-related studies listing has been changed over to a modernized version. All the links have been updated accordingly.
TAG’s 2023 Research Toward a Cure and Immune-Based Therapies Pipeline Report is completed and will be posted online by this Friday, immediately ahead of IAS 2023, the 12th IAS Conference on HIV Science in Brisbane.
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