The ACTG (AIDS Clinical Trials Group) has announced the commencement of the ACACIA study (Antiretrovirals Combined with Antibodies for HIV-1 Cure in Africa), also known as A5417, a Phase 2, double-blind, randomized clinical trial. The study will evaluate the safety, virologic, and immunologic effects of two long-acting broadly neutralizing antibodies (bNAbs), 3BNC117-LS and 10-1074-LS, when administered at the initiation of antiretroviral therapy (ART) in adults living with HIV in several African countries.
The ACACIA trial is designed as a multi-center study and plans to enroll 135 participants aged 18 to 60 who are living with HIV but not yet receiving treatment. Participants will begin an integrase inhibitor-based ART regimen and be randomized in a 2:1 ratio to receive either a single intravenous infusion of 3BNC117-LS and 10-1074-LS or placebos. The trial will take place in Botswana, Malawi, South Africa, and Zimbabwe.
Study Design and Objectives
ACACIA is designed to complement ACTG’s PAUSE study, which is evaluating similar bNAbs in individuals with HIV who have achieved viral suppression through ART. Both ACACIA and PAUSE incorporate an analytic treatment interruption (ATI), a carefully monitored pause in ART, which is crucial for assessing whether an intervention can control HIV without ongoing ART.
According to Wadzanai Samaneka, M.B.Ch.B., M.Sc., Co-Chair of ACACIA from the University of Zimbabwe, the study is designed to ensure that participants receive bNAbs in a way that optimizes their potential therapeutic benefit when the level of virus is at its highest. The study design also ensures that the bNAbs will be at very low levels or cleared from the blood prior to beginning ATI, so that the antiviral activity of the bNAbs does not interfere with our ability to detect a long-lasting immunologic effect of the bNAbs.
Analytic Treatment Interruption (ATI)
Participants in the ACACIA trial who achieve HIV-1 RNA levels below 200 copies/ml and a CD4+ T cell count of 450 cells/mm3 or higher will undergo ATI 15 months after the initial bNAb administration, once antibody levels are very low or undetectable. During the ATI, participants will be closely monitored for 24 weeks and may remain off ART for up to 72 weeks if they maintain viral suppression. ART will be restarted if specific criteria are met, such as a CD4 count decline below 350 copies/μL for two consecutive measurements or a viral load increase to at least 1000 copies/mL for four consecutive weeks.
Significance of the Study
Joseph J. Eron, M.D., ACTG Chair from the University of North Carolina, stated, "We are excited to announce a second HIV cure trial taking place in Africa, as part of ACTG’s commitment to conducting HIV cure research among global populations of people living with HIV. This is one of the first studies of bNAbs administered at the time of ART initiation in Africa and we are eager to gain insights into the approach in this setting."
The ACACIA trial is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and co-funded by the Bill & Melinda Gates Foundation. The bNAbs are manufactured by Celldex Therapeutics and supplied by the Rockefeller University.
