A GROUNDBREAKING Phase IIa HIV cure study in South Africa has demonstrated the safety and potential efficacy of a novel therapeutic regimen in women with acute HIV infection, marking a critical step toward HIV remission strategies in populations often underrepresented in clinical trials.
The study enrolled 20 women from the Females Rising through Education, Support, and Health (FRESH) cohort, all of whom had been on suppressive antiretroviral therapy (ART) for at least 12 months and were sensitive to at least one broadly neutralising antibody (bNAb). Participants received up to 10 doses of the toll-like receptor 7 (TLR7) agonist vesatolimod (VES) alongside intravenous infusions of two bNAbs, VRC07-523LS and CAP256V2LS. An analytical treatment interruption (ATI) began on day 35, allowing researchers to assess viral rebound and time to ART restart, with participants remaining off ART until day 336 or until predefined virologic thresholds were reached.
All 20 participants received the study treatment and commenced ATI, with no serious treatment-related adverse events reported. One participant discontinued VES due to mild cytokine release syndrome, while 18 experienced infusion-related reactions that resolved within 2 days. Five participants completed the 43-week ATI without requiring ART restart, two of whom maintained viral suppression below 50 copies/mL. Fourteen participants met ART restart criteria, and one remained in ATI at the study’s last assessment. Notably, eight individuals exhibited partial virologic control with fluctuating viral loads, suggesting potential immune-mediated viral suppression.
This study provides crucial evidence that complex HIV cure trials can be successfully conducted in resource-limited settings, offering a pathway toward novel remission strategies in African women. The safety and tolerability of VES, VRC07-523LS, and CAP256V2LS, alongside promising virologic control in some participants, support further investigation into mechanisms driving immune-mediated HIV suppression.
Ada Enesco, EMJ
Reference
Dong K et al. Evaluation of 2 bNAbs plus vesatolimod in early-treated south African women with HIV-1 during ATI. Abstract 2240. Conference on Retroviruses and Opportunistic Infections, 9-12 March 2025.
