Introduction: Cervical cancer remains the second most common cancer among women worldwide, with 85% of cases occurring in low-and middle-income countries (LMIC). Women living with HIV (WLWH) are at a particularly high risk of developing for high-grade cervical intraepithelial neoplasia (CIN2/3) and cervical cancer, and the standard surgical treatment is far less effective in this population. Thus, research on medical therapies and combination treatment options remain a priority. In preparation for a clinical trial involving adjuvant intravaginal 5-fluorouracil (5FU) cream following surgical treatment for CIN2/3, we explored the acceptability of our proposed intervention among WLWH and male partners. Methods: We conducted qualitative interviews with WLWH and male partners in Johannesburg, South Africa between April 2022 and September 2022. We invited WLWH to participate in semi-structured focus group discussions (FGDs), while male partners were invited to participate in semi-structured in-depth interviews (IDIs). The analysis utilized a rapid, deductive approach in which quotations were identified and categorized into relevant domains: factors affecting cervical cancer screening, the initiation of 5FU vaginal cream, and adherence to 5FU. Results: We conducted 9 FGDs comprising 48 WLWH and 18 IDIs with male partners. The mean age of participants was 43 years, and the majority (75%) had completed secondary education. Most women (75%) had also undergone Pap smear screening and 50% had a prior abnormal Pap smear. Qualitative analysis revealed that education on HPV and cervical cancer, prior experience with the health system, and social perceptions/stigma influenced cervical cancer screening uptake and were important factors in the initiation of and adherence to 5FU. Mens knowledge about cervical cancer was extremely limited. Overall, participants perceptions of the proposed trial intervention were positive, with most participants expressing confidence that women would be able to use and adhere to the intravaginal 5FU cream. Concerns raised included possible effects of 5FU on fertility, contraceptive requirements, and the recommendation for brief periods of abstinence following cream use to prevent partner side effects. Conclusions: Although participants had some cervical cancer knowledge, misperceptions about HPV and cervical cancer were common and prevented follow-up for abnormal Pap results. Participants emphasized the need for thorough counseling about 5FU, citing this as integral for uptake. Utilizing stakeholder input to design the clinical trial is necessary to promote acceptability and adherence to the trial intervention.

The authors have declared no competing interest.

CJC and LR are funded by the United States National Institutes of Health (NIH) to study combination treatment approaches for cervical precancer in women living with HIV (R01 CA250850). Trainee support for NST was provided by NIH (T32 HD075731) and MJB was also supported by NIH through the NC Translational and Clinical Sciences (NC TraCS) Institute (UM1TR004406). The NIH was not involved in the conduct of the study, interpretation of its results, or our decision to submit results for publication.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Prior to conducting this study, we obtained ethical approval from the University of Witwatersrand Human Research Ethics Committee (M200543) and the University of North Carolina at Chapel Hill Institutional Review Board (20-1227).

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All data produced in the present study are available upon reasonable request to the authors