Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among Women Living with HIV in South Africa: Primary Outcomes from the ACT 2 Randomized Trial.

Objective: Determine acceptability and feasibility of loop electrosurgical excision procedure (LEEP) combined with adjuvant intravaginal 5-fluorouracil (5FU) for treatment of cervical intraepithelial neoplasia grade 2/3 (CIN2/3) in women living with HIV (WLWH). Design: Double-blind, randomized, placebo-controlled Phase 2b feasibility trial. Setting: Public-sector hospital in Johannesburg, South Africa. Population: 180 WLWH aged 18+ years with CIN2/3 confirmed by LEEP and on antiretroviral therapy for ≥60 days. Methods: Participants underwent LEEP and were randomly assigned (1:1) to receive 8 doses of adjuvant 5FU or placebo cream every other week and followed for 24 weeks. Main Outcome Measures: The primary outcomes were acceptability and feasibility (adherence, retention, safety, tolerability). Results: Between March 2023 and January 2025, we randomized 180 WLWH. Median age was 41 years (interquartile range [IQR]: 35-45), median CD4+ count was 636 cells/mm Conclusions: LEEP plus adjuvant intravaginal 5FU is acceptable and feasible among WLWH in South Africa, supporting progression to a Phase 3 trial. Clinical Trial Registration: NCT05413811.