ACTG Launches First HIV Cure Clinical Trial in Africa

The AIDS Clinical Trials Group (ACTG), an international clinical trials network specializing in HIV and other infectious diseases, has initiated the PAUSE study, a groundbreaking HIV cure clinical trial taking place in Africa. The study, also known as A5416/HVTN 806/HPTN 108, is a phase 1, double-blind, randomized trial designed to evaluate the safety and efficacy of two long-acting broadly neutralizing antibodies (bNAbs), 3BNC117-LS-J and 10-1074-LS-J, in comparison to a placebo. This trial involves adults living with HIV who will temporarily halt their antiretroviral therapy (ART) while under strict medical supervision.

Although ART is highly effective in managing HIV, it does not offer a cure. Individuals must continue ART indefinitely to suppress viral replication and maintain immune health. Even with ART, dormant HIV reservoirs remain in immune cells, ready to multiply if ART is stopped, leading to increased viral loads. The PAUSE study aims to explore a new intervention strategy that could enable the immune system to manage HIV without ART for extended periods.

Dr. Judith Currier, Chair of ACTG and a prominent figure at the University of California Los Angeles, emphasized the importance of conducting HIV cure research among diverse global populations. She noted that the HIV epidemic varies significantly between African countries and the United States, with differences in viral subtypes, age, gender distribution, and co-morbidities. By conducting the study in Africa, researchers hope to gain valuable insights to optimize HIV cure strategies in regions with the highest HIV burden.

The PAUSE trial will enroll 48 participants aged 18 to 70 who have achieved viral suppression on ART. At least 40 percent of the participants will be cisgender women. Participants will be randomly assigned in a two-to-one ratio to receive either a single infusion of 3BNC117-LS-J and a single infusion of 10-1074-LS-J, or a placebo for both. Two days after the infusion, participants will discontinue their ART. They will be closely monitored over 24 weeks during this treatment interruption. If they maintain viral suppression, they may remain off ART for up to 72 weeks. Participants will resume ART if their CD4 count drops below 350 copies/μL or if their viral load exceeds 1000 copies/mL for four consecutive weeks, among other criteria.

Dr. Mina Hosseinipour, Co-Chair of the PAUSE study and a researcher at the University of North Carolina (UNC) project in Malawi, highlighted the potential of the two bNAbs, which have shown promise in earlier research. The study aims to determine their tolerance, effectiveness in maintaining viral suppression without ART, and their impact on the size of the latent HIV reservoir.

The PAUSE study is being conducted in collaboration with the HIV Vaccine Trials Network (HVTN) and the HIV Prevention Trials Network (HPTN). It is open to selected research sites within these networks in Africa. Dr. Larry Corey of HVTN expressed enthusiasm for the progress and application of past research on broadly neutralizing antibodies in South Africa to this new protocol.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), sponsors the PAUSE study. Additional funding comes from the Bill & Melinda Gates Foundation. The bNAbs used in the study are manufactured by Just-Evotec and supplied by Rockefeller University.

Dr. Marina Caskey from Rockefeller University and Weill Cornell Medicine, and Vice-Chair of PAUSE, emphasized the importance of ensuring that HIV cure strategies are effective across diverse populations. The study's development involved early engagement with local investigators and communities living with HIV to address their needs and challenges.

Led by Dr. Hosseinipour and Dr. Rebone Maboa of The Aurum Institute, with Dr. Caskey and Dr. William Hahn of Fred Hutch Cancer Center as Co-Vice Chairs, this innovative trial continues ACTG's mission to advance HIV cure research. Dr. Currier and Dr. Joseph J. Eron of UNC lead ACTG, which has been at the forefront of HIV and infectious disease research since 1987.