ACTG Launches Second HIV Cure Clinical Trial in Africa

ACACIA Study Is Evaluating Two Long-Acting Broadly Neutralizing Antibodies Given at HIV Treatment Initiation

/EIN News/ -- LOS ANGELES, Jan. 21, 2025 (GLOBE NEWSWIRE) -- ACTG, a global clinical trials network focused on HIV and other infectious diseases, today announced the opening of the ACACIA study (Antiretrovirals Combined with Antibodies for HIV-1 Cure in Africa), also known as A5417. ACACIA is a phase 2, double-blind, randomized study evaluating the safety and virologic and immunologic effects of the two long-acting broadly neutralizing antibodies (bNAbs) 3BNC117-LS and 10-1074-LS when given at the start of antiretroviral therapy (ART) to adults living with HIV in four African countries.

This study complements ACTG’s PAUSE study, which is evaluating two very similar bNAbs among people living with HIV who have been virally suppressed on ART and enrolled the first participant in June 2024.

Participants in ACACIA and PAUSE will undergo an analytic treatment interruption (ATI) – a closely monitored pause in ART. ATIs are an integral part of HIV cure trials, because they enable researchers to understand whether an intervention can help to control HIV in the absence of ART. While ART can suppress the virus, it cannot cure HIV and requires life-long adherence. Even when taking ART, people living with HIV have latent (or hidden) HIV reservoirs (groups of immune cells that contain HIV but do not produce new copies). When people stop taking ART, virus in the latent cells begins to multiply, thereby increasing the amount of HIV in a person’s body.

“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,” said ACTG Chair Joseph J. Eron, M.D., University of North Carolina. “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.”

ACACIA is a multi-center trial that will enroll 135 participants between the ages of 18 and 60 who are living with HIV and not yet receiving HIV treatment. All participants will begin taking an integrase inhibitor-based ART regimen. At the same time, they will be randomized in a two-to-one ratio to receive either a single intravenous infusion of 3BNC117-LS and a single intravenous infusion of 10-1074-LS or placebos for these bNAbs (administered on day one). Because these bNAbs are expected to remain in the body for many months, participants who have HIV-1 RNA <200 copies/ml and CD4+ T cell count of ≥450 cells/mm³ will stop taking ART and begin their ATI 15 months later, after the antibodies have reached very low to undetectable levels in blood. Participants will be closely monitored during ATI over the course of 24 weeks. If they remain virally suppressed after that, they may remain off ART for up to a total of 72 weeks. Participants will restart ART when they meet the criteria to do so, including a CD4 count decline to below 350 copies/μL for two consecutive measurements or an increase in viral load to at least 1000 copies/mL for four weeks in a row, among others.

“We have designed ACACIA to ensure that participants receive the bNAbs in a way that optimizes their potential therapeutic benefit when the level of virus is at its highest,” said ACACIA Co-Chair Wadzanai Samaneka, M.B.Ch.B., M.Sc., University of Zimbabwe. “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.”

ACACIA is open to select ACTG sites in Botswana, Malawi, South Africa, and Zimbabwe. It is sponsored by the National Institute of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID, which also funds ACTG) under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. The study is co-funded by the Bill & Melinda Gates Foundation. The bNAbs were manufactured by Celldex Therapeutics and are being supplied by the Rockefeller University.

ACACIA is led by Trevor Crowell, M.D., Ph.D., U.S. Military HIV Research Program, and Dr. Samaneka (Co-Chairs) and Marina Caskey, M.D., the Rockefeller University and Weill Cornell Medicine, and Katharine Bar, M.D., University of Pennsylvania (Co-Vice Chairs). ACTG is led by Dr. Eron and Rajesh T. Gandhi, M.D., Massachusetts General Hospital and Harvard Medical School (ACTG Vice-Chair).

For more information about ACACIA, please visit clinicaltrials.gov.

About ACTG
ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve.

Disclaimer: This content is solely the responsibility of ACTG and does not necessarily represent the official views of the NIH.

Media Contact:
Jenna Conley, ACTG
jenna@conleycommunications.net