ACTG Initiates HIV Cure Trial with Innovative Immune Therapies

A new phase 1/2a clinical trial, designated A5374, has been launched by ACTG, a renowned global network that conducts clinical trials with a focus on HIV and infectious diseases. This study, known as "Triple Immune Strategy for HIV Remission," aims to investigate the safety, tolerability, and antiviral efficacy of a unique therapeutic combination. This combination includes T-cell vaccines, two types of broadly neutralizing antibodies (bNAbs), and an immune-boosting treatment for individuals with HIV who began antiretroviral treatment (ART) early in their infection.

The trial is a multi-site, randomized, and placebo-controlled endeavor that seeks to understand whether the novel regimen can provide extended periods of viral control during an analytical treatment interruption, a pause in ART that is closely supervised. Unlike current ART, which only manages HIV and requires lifelong use, the strategy in A5374 is a potential step towards enabling the immune system to handle HIV without continuous ART for extended periods.

Judith Currier, M.D., M.Sc., Chair of ACTG and a representative from the University of California Los Angeles, highlighted the expectation that a combination of innovative treatments will be necessary to reduce HIV-carrying cells and stimulate the immune system to prevent viral replication. The trial, which is crucial for future research, will enroll 45 participants aged 18 and above who initiated combination ART shortly after an acute HIV diagnosis. The study is designed to last for approximately two years per participant.

Participants will continue their HIV medications and will receive either the new treatment series or a placebo. The innovative treatment plan includes a T-cell vaccine regimen, two bNAbs, and an immune booster. After approximately 16 months, participants will discontinue ART and be closely observed for any changes in HIV viral load and CD4 T-cell counts. They will resume ART if there are signs of HIV resurgence or if they become pregnant. The study's objective is to compare the duration of viral control between the active treatment group and the placebo group during the treatment interruption.

The A5374 study is set to take place at up to 10 sites across the United States and Brazil, and is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH). The University of Oxford is responsible for supplying the T-cell vaccines and conducting endpoint assays, while Gilead Sciences provides the bNAbs and TLR7 agonist.

The trial is led by Dr. Sharon A. Riddler, M.D., M.P.H., from the University of Pittsburgh, along with Cynthia L. Gay, M.D., M.P.H., from the University of North Carolina, and John Mellors, M.D., also from the University of Pittsburgh. ACTG is directed by Dr. Currier and Joseph J. Eron, M.D., from the University of North Carolina. Further details about the trial can be found on clinicaltrials.gov.

The ACTG, established in 1987, is the largest and longest-running clinical trials network dedicated to HIV and other infectious diseases, funded by NIAID and collaborating NIH institutes. It conducts research to enhance HIV management, develop a cure, and innovate treatments for tuberculosis, hepatitis B, and emerging diseases. The network is made up of thousands of researchers, staff, and community members working at 65 locations across four continents, with the ultimate aim of advancing science to significantly impact the lives of those affected by infectious diseases.