A Dual Prevention Pill for HIV & Pregnancy Prevention: A Pilot Study Among Adolescent Girls and Young Women in...

Adolescent girls and young women (AGYW) in sub-Saharan Africa are at risk for HIV/unintended pregnancy. Adherence and continuation to effective oral pre-exposure prophylaxis (PrEP) are limited in AGYW. We hypothesized that an over-encapsulated dual prevention pill (DPP) combining PrEP + oral contraceptive (OC) would be preferred, acceptable, and improve adherence compared to PrEP alone. We randomized HIV-uninfected, 16-24 year-olds 1:1 to use DPP or 2-pill regimen (2PR -PrEP and OCs separately) for three 28-day cycles each. We compared preference for DPP vs. 2PR (exact binomial test) and regimen effects on four acceptability domains: use attributes, product attributes, side effects, impact on sex (Wilcoxon signed-rank tests). Adherence was compared by regimen and sequence (mixed-effects logistic regression) using self-report, pill-count, tenofovir-diphosphate levels in dried blood spots (DBS), indicating ≥ 4 doses per week(≥ 500 fmol/punch at Month 1 and ≥ 700 fmol/punch at Months 2-6). 26/30 participants (mean age 19.4years) completed the study (Nov 2022-Sept 2023). 62% preferred DPP, 38% 2PR (p = 0.24). Most rated both regimens as acceptable, with no differences between them (all p > 0.05). Adherence was high by self-report (98%) and pill-count (97%), but low based on DBS results (DPP: mean 392 fmol/punch, 2PR: mean 384 fmol/punch); with only 10% consistently adherent. There was no difference in adherence by regimen, though odds were higher in period 1 vs. 2 (AOR 3.7; 95% CI 1.10-12.8). Both regimens were safe; 2 pregnancies occurred during the DPP regimen, with no HIV seroconversions. No significant differences in preference, acceptability, and adherence between DPP and 2PR were found in this study. Adherence was low and waned over time. A larger study with a smaller co-formulated DPP may better inform its impact on HIV and pregnancy prevention.The study has been registered at ClinicalTrials.gov Identifier NCT04778514.