Factors associated with women’s preference for an over-encapsulated Dual Prevention Pill: Findings from two clinical crossover trials among women in South Africa and Zimbabwe

Background A dual prevention pill (DPP) for co-delivery of pregnancy and HIV prevention is currently in development and will offer an alternative to taking two separate products. We examined behavioral, partnership/interpersonal, social, and structural correlates of preferences for an over-encapsulated DPP (as a proxy for the product in development, consisting of oral contraceptive pill and oral PrEP pill) among women and adolescent girls in South Africa and Zimbabwe to inform DPP introduction and counseling strategies. Methods This secondary analysis used data from two clinical crossover studies that compared the acceptability, adherence, and preference for the over-encapsulated DPP versus separate PrEP and oral contraceptives. HIV-uninfected, non-pregnant cisgender women were enrolled in Johannesburg, South Africa (n = 96, ages 18–40) and Harare, Zimbabwe (n = 30, ages 16–24). Participants were randomized 1:1 to use either DPP or two separate pills for three 28-day cycles, then switched. Preferences were measured at the end of crossover and via exit in-depth interviews. Results The mean age was 27 years in South Africa and 19 years for Zimbabwe. Most participants had completed secondary school. Childbearing was more common in Zimbabwe (97%) than South Africa (74%). Pregnancy prevention was highly valued in both sites (~ 90%), but Zimbabwean participants voiced greater concern about HIV. DPP preference was higher in Zimbabwe (62%) than South African (39%). In South Africa, DPP preference was associated with behavioral factors (anal sex, experience of sexual violence, relationship conflict, and transactional relationships/sex) and product characteristics (ease of use, side effects). In Zimbabwe, concern about HIV acquisition, interpersonal power, and structural factors (i.e., food insecurity and housing security) were associated with DPP preference. Qualitative interviews highlighted the DPP’s simplicity as key advantage over two separate pills, though participants desired a smaller DPP and more discreet packaging to reduced stigma and ease use. Conclusions While women in both countries value integrated HIV and pregnancy prevention, distinct demographic, behavioral, and social factors influence DPP preference. Tailoring DPP introduction and support strategies to address specific challenges—such as relationship dynamics and product usability—may optimize the acceptance and effectiveness of dual prevention strategies. Trial registration: ClinicalTrials.gov, Zimbabwe: NCT04778514; South Africa: NCT04778527.