Background
Antiretroviral therapy (ART) can reduce morbidity and mortality but does not eradicate HIV. Developing new therapies that induce HIV remission is crucial to end the epidemic. African women bear a disproportionate burden of the global epidemic yet are rarely included in clinical trials. We conducted a phase 2a HIV cure study to evaluate the safety of a regimen of 2 broadly neutralizing antibodies (bNAbs), VRC07-523LS and CAP256V2LS, and a TLR7 agonist, vesatolimod (VES), in acutely treated women with HIV-1 in South Africa (NCT05281510).
Methods
Twenty women from the Females Rising through Education, Support, and Health (FRESH) acute HIV infection cohort, who were suppressed on ART for ≥12 months and sensitive to at least 1 bNAb, were enrolled. Participants received up to 10 oral doses of VES (6 mg, dose escalation to 8 mg) every 2 weeks starting on day 0 and IV infusions of VRC07-523LS (20 mg/kg) and CAP256V2LS (20 mg/kg) on day 7. Participants began an analytical treatment interruption (ATI) on day 35 and remained off ART until day 336 or until they met ART restart criteria (HIV-1 RNA ≥1000 copies/mL for 8 consecutive weeks and without a drop of 0.3log10; or confirmed HIV-1 RNA >100,000 copies/mL; or confirmed CD4 count <350 cells/µL). The primary endpoint was safety. Secondary endpoints included time to viral rebound (HIV-1 RNA >200 copies/mL), time to ART restart, and pharmacokinetics.
Results
As of September 18, 2024, all 20 participants had received study treatment and started ATI. There were no treatment-related serious adverse events. One participant experienced grade 1 cytokine release syndrome that led to discontinuation of VES. Eighteen experienced infusion-related reactions (16 grade 1; 2 grade 2); all resolved within 2 days. Five participants completed the 43-week ATI without meeting ART restart criteria, 2 of whom were completely suppressed (HIV-1 RNA <50 copies/mL); 14 met ART restart criteria; and 1 remained in ATI. Eight participants had evidence of partial virologic control with oscillating rebound, characterized by fluctuating levels of viremia with periods of undetectable viral load.
Conclusions
This first-in-Africa HIV cure trial demonstrates that complex cure studies can be successfully conducted in resource-limited settings with great unmet need. VES, VRC07-523LS, and CAP256V2LS were safe and well tolerated in acutely treated South African women. Potential mechanisms for the variable patterns of virologic control observed in this novel study are under investigation.
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