Feasibility of Intravaginal Artesunate as an Adjuvant HPV & Cervical Precancer Treatment Among Women Living With HIV in Kenya: Study Protocol for a Phase II Clinical Trial.

IntroductionCervical cancer disproportionately affects women in low- and middle-income countries (LMICs), who account for 90% of deaths from the disease. Human papillomavirus (HPV) is responsible for 99% of cervical cancer cases. Women living with HIV (WLWH) have a higher risk of persistent HPV infection and a greater likelihood of developing cervical cancer. Prevention of cervical cancer requires effective screening and precancer treatment programs. In LMICs, the common treatment method for cervical precancer is thermal ablation. However, for WLWH, thermal ablation is associated with high rates of persistent HPV infection following treatment, a key risk factor for precancer recurrence. Adjuvant topical treatments with cytotoxic or antiviral properties may reduce HPV persistence following ablation. Preclinical and early-phase clinical trials indicate that topical artesunate is active against HPV-associated anogenital lesions, including cervical precancer, and can induce HPV clearance. Consequently, intravaginal artesunate may improve HPV clearance following thermal ablation, although no clinical trials have investigated this.MethodsWe are conducting a phase II, double-blind, randomized, placebo-controlled trial among 120 HIV seropositive women in Kenya to investigate the feasibility of self-administered intravaginal artesunate pessaries as adjuvant therapy following thermal ablation treatment for cervical precancer. The primary outcome is type-specific HPV clearance 6 months after randomization. Secondary outcomes are safety, adherence, acceptability, uptake, and retention. Participants will be enrolled at least 4 weeks after ablation and will self-administer pessaries on weeks 1, 3, and 5, with alternating drug-free weeks. Study follow-up will extend to 24 weeks after randomization.ConclusionHigh rates of persistent HPV infection in WLWH is a key limitation of thermal ablation, the most accessible cervical precancer treatment in LMICs. This trial will investigate the feasibility of repurposing topical artesunate as an adjuvant therapy to improve HPV clearance following thermal ablation in WLWH.Trial RegistrationClinicalTrials.gov identifier: NCT06519994.