Women living with HIV are up to six times more likely to get cervical cancer. Cervical cancer screening can identify early changes in the cervix (known as precancer), which can be treated at this early stage. Among women with HIV, the current treatment methods for cervical precancer are not completely effective. Up to 30% of women can continue to have precancer after treatment – known as treatment failure. Because of this, scientists are investigating methods to improve the current cervical precancer treatment methods for women living with HIV. Previous studies in other countries have shown that a medication known as 5-FU, which is available as cream and used to treat skin precancer or cancer, can be used intravaginally after initial cervical precancer treatment in HIV-positive women, to reduce treatment failure. 

This study seeks to investigate whether a generic, commonly available chemotherapeutic drug which available as a cream, known as Fluorouracil (5-FU), can be used off-label by women with HIV as an additional, self-administered, intravaginal treatment after the currently approved treatment methods, to reduce cervical precancer treatment failure. The study aims to investigate whether intravaginal 5FU used in this manner is safety, whether many women will want to use it (uptake & acceptability), whether side effects will be few as it has been shown in other studies (tolerability), and whether women will use the medication as instructed (adherence). This study will last approximately 20 weeks. Women who are enrolled in the study will apply the study medication (5% 5-FU cream) inside the vagina before sleeping once every other week, and they will visit the study clinic on alternative weeks to be monitored for any side effects. Women in the study will keep a calendar of when they use the medication and will write down any symptoms or side effects they have (using a symptom diary), if they are able to read and write. Additionally, all women in the study will be called weekly by a research assistant to report any symptoms they have. Any study participant with concerning symptoms will be seen by a study clinician, and all costs will be covered by the study. At the end of the study, women will be asked about their experience with using the intravaginal treatment. The information obtained from this study will be used to understand whether 5% 5FU cream can be used off-label widely by more women with HIV following precancer treatment in Kenya and the rest of Africa and the world to improve the effectiveness of current precancer treatment methods. 

Women living with HIV face up to six times increased risk of cervical cancer, and cervical cancer is a leading cause of death in this population. Current approved treatment for high-grade cervical precancer, scientifically termed cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3), is either ablation (cryotherapy or thermal ablation) or excision. Both treatment methods are associated with high rates of CIN2/3 treatment failure in women with HIV,  up to 30% at one year. Studies in high-income countries have demonstrated that off-label use of self-administered, intravaginal 5% 5-FU cream following primary CIN2/3 treatment in HIV-positive women can reduce treatment failure. 

This is a single arm pilot study investigating the safety, uptake, tolerability, adherence, and acceptability of off-label self-administered intravaginal 5% fluorouracil (5-FU) cream as adjuvant therapy following primary treatment for CIN2/3 among women living with HIV in Kenya.  Fourteen participants will be enrolled. Participants will self-administer 2 grams of 5% 5-FU cream intravaginally biweekly (every other week, on weeks 1, 3, 5, 7, 9, 11, 13, 15) for a total of 8 applications, and will return to the clinic on weeks 2, 4, 6, 8,10, 12, 14, and 16 for safety and adherence assessments, including a pelvic exam by a trained clinician. Our hypothesis is that adjuvant, self-administered 5% 5-FU cream, used intravaginally at the proposed dose and frequency will be safe, tolerable, and acceptable for use among this population. Our hypothesis is that adjuvant, intravaginal, self-administered 5% 5-FU cream at the proposed dose and frequency will be safe, tolerable, and acceptable for use among this population. This trial, together with data from other studies, will support proceeding to a randomized phase II or phase III trial in Kenya to investigate whether this intervention will reduce CIN2/3 recurrence as has been demonstrated in other settings.