Safety and Adherence of Self-Administered 5-Fluorouracil Cream After CIN Treatment in HIV-Positive

Purpose: Innovative and feasible strategies are needed to improve cervical intraepithelial neoplasia grade 2/3 (CIN2/3) treatment among women living with HIV (WLWH), the majority of whom live in Sub- Saharan Africa and face up to 30% recurrence following ablation or excision treatment. Studies in high- income countries have demonstrated that self-administered intravaginal 5-Fluorouracil (5FU), a generically available antimetabolite, can be safely used for CIN treatment among both HIV-negative and positive women. We investigated the feasibility of self-administered intravaginal 5FU cream following CIN2/3 treatment in a Phase I trial (NCT05362955) among WLWH in Kenya. Methods: Twelve WLWH in Kisumu, Kenya, with biopsy-confirmed CIN2/3 who had undergone primary treatment with ablation or excision were enrolled. Participants self-administered 2g of 5% 5FU cream intravaginally using graded applicators once every two weeks (eight applications), applying it nightly at home, and attended clinic visits in intervening weeks for safety monitoring. The primary objective was safety, assessed using a standardized grading scale. Secondary objectives were tolerance, adherence, and acceptability. Adherence was assessed via self-report and inspection of returned applicators, while acceptability was evaluated through a questionnaire and in-depth interviews (IDIs), analyzed thematically. Results: The mean age and CD4 count were 43.9 years and 781 cells/mm3, respectively. Most participants (58%) had completed less than an 8th-grade education. All reported mild (grade 1) adverse events (AEs)—most commonly increased vaginal discharge (29.7%), irritation (12.2%) and dryness (10.8%), lasting 1–5 days. Provider-observed AEs included grade 1 cervical erythema and superficial epithelial disruptions. All participants tolerated eight 5FU doses, and 96% adherence was demonstrated. Acceptability was high, with all participants noting that they would recommend the treatment to others. Qualitative data indicated high acceptability due to ease of use, the discrete nature, and the comfort of home application. Challenges encountered included correctly measuring the study drug, finding a private place at home to self-administer, and the need to use condoms during treatment. Conclusion: Self-administered intravaginal 5FU was safe and demonstrated high adherence and acceptability. Randomized trials are needed to determine its efficacy in improving CIN2/3 outcomes in African WLWH. Citation Format: Chemtai Mungo, Jackton Omoto, Elizabeth Bukusi, Cirilus Ogollah, Gershon Rota, Lisa Rahangdale. Safety of and Adherence to Self-Administered Intravaginal 5-Fluorouracil Cream Following High-Grade Cervical Intraepithelial Neoplasia (CIN) 2/3 Treatment Among HIV-Positive Women in Kenya: A Pilot Trial [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 66.