Women living with HIV (WLWH) face up to six times increased risk of cervical cancer. As a result, cervical cancer is a leading cause of death in this population. Cervical cancer is caused by infection with the human papillomavirus (HPV), resulting in precancerous changes that, if not adequately treated, progress to cancer. Thermal ablation is a commonly used treatment for cervical precancer in Kenya and other low- and middle-income countries (LMICs). Current treatments for HPV or cervical precancer in WLWH, including thermal ablation, are associated with high rates of treatment failure. In a recent study, only 44% of WLWH had cleared HPV at six months following thermal ablation, putting them at risk of cervical precancer and cancer despite treatment.

The objective of this Phase II, randomized, placebo-controlled trial is to evaluate whether use of intravaginal artesunate pessaries (vaginal inserts) can be used as an additional (adjuvant) therapy following thermal ablation to improve HPV clearance. The study will evaluate whether women who use artesunate will have higher HPV clearance at 6 months, compared to those who used a placebo. The study will also evaluate safety, adherence, and acceptability of this treatment. 120 participants will be enrolled in the study. Participants will self-administer the study drug nightly for 5 days, take a week off, and repeat twice (use study drug on week 1, 3 ,5) and will return to clinic on weeks 2, 4, 6, 12 and week 24 for follow-up.

Background: Women living with HIV (WLWH) face up to six times increased risk of cervical cancer, as a result cervical cancer is a leading cause of death in this population. Cervical cancer is caused by persistent infection with the human papillomavirus (HPV), resulting in precancerous changes that if not adequately treated, progress to cancer. Thermal ablation is a commonly used treatment for cervical precancer in Kenya and other low- and middle-income countries (LMICs). Current treatments for HPV or cervical precancer, including thermal ablation, are associated with high rates of treatment failure in WLWH. In a recent study from Zambia, only 44% of WLWH had cleared HPV at six months following thermal ablation treatment. Other studies have demonstrated up to 30% recurrence rate of high-grade cervical precancer at 12 to 24 months after treatment.

Objectives: The objective of this Phase II, randomized, placebo-controlled trial is to evaluate whether intravaginal artesunate pessaries (vaginal inserts) can be used as adjuvant therapy following thermal ablation to improve HPV treatment outcomes in WLWH. The primary outcome is high-risk HPV clearance at 6-months in the artesunate versus placebo arm. Secondary outcomes include safety, adherence, acceptability, and feasibility (recruitment, accrual, and retention).

Methods: 120 participants will be enrolled in the study, randomized 2:1 to artesunate versus placebo. Participants will self-administer the study drug nightly for 5 days, take a week off, and repeated 2 times (study drug application on weeks 1, 3, 5), and will return to the clinic on weeks 2, 4, 6, 12, and week 24 for follow-up. The study duration is 6 months. Safety and adherence will be assessed through a review of symptoms and biweekly follow-up during the treatment phase. Acceptability will be evaluated at week 6, and hrHPV clearance at week 24. Data collection will be via an electronic database. Data analysis will be quantitative. Our Hypothesis is that adjuvant, self-administered artesunate pessaries will improve HPV clearance following thermal ablation among WLWH and will be safe, acceptable, and associated with high adherence rates. This trial will support a future Phase III randomized trial to evaluate the efficacy of adjuvant intravaginal artesunate following thermal ablation in reducing CIN2/3 recurrence in WLWH.