Factors associated with women’s preference for an over-encapsulated dual prevention pill: findings from South Africa and Zimbabwe

Abstract 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, interpersonal partnership, social, and structural correlates of preferences for an over-encapsulated DPP (as a proxy for the co-formulated product under development/testing, consisting of oral contraceptive pill and oral HIV prevention pre-exposure prophylaxis (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 trials that compared the acceptability, adherence, and preference for the over-encapsulated DPP versus separate PrEP and oral contraceptives. HIV-negative, 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, while childbearing experience was more common in Zimbabwe (97%) than in 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 in South Africa (39%). In South Africa, bivariate analysis showed that DPP preference was associated with behavioral factors (no anal sex experience, ever experience of sexual violence, relationship conflict, and transactional relationships/sex) and product characteristics (ease of use, side effects), although only anal sex and relationship control remained significant in the multivariable model. In Zimbabwe, concern about HIV acquisition (but in the opposite direction), interpersonal power, structural factors (i.e., more food insecurity and less housing insecurity), and ease of use were associated with DPP preference in bivariate analyses (no multivariable analysis was possible). Qualitative interviews highlighted the DPP’s simplicity as a key advantage over two separate pills, though participants desired a smaller DPP and more discreet packaging to reduce stigma and ease use. Conclusions While women in both countries value integrated HIV and pregnancy prevention, distinct behavioral and social factors, and product attributes influence DPP preference. Tailoring DPP introduction and support strategies to address specific challenges—such as relationship dynamics and product usability—may support acceptability and informed choice of dual prevention strategies. Trial registration ClinicalTrials.gov, Zimbabwe: NCT04778514 (02/25/2021); South Africa: NCT04778527 (02/25/2021).