Understanding trial designs and acceptability of participation in an HIV vaccine trial with concurrent randomisation to oral pre-exposure prophylaxis in East and Southern Africa: a longitudinal qualitative study

Introduction: This qualitative study was conducted to assess participants’ understanding of the PrEPVacc trial design and factors that influenced decisions to participate in the trial. PrEPVacc was a phase IIb, three-arm, two-stage HIV prophylactic vaccine trial with a second randomisation to oral pre-exposure prophylaxis. The main objective was to assess the safety and efficacy of two HIV-1 prophylactic vaccine regimens, each compared to placebo, in preventing the acquisition of HIV. Methods: Using a longitudinal approach, qualitative data were collected between October 2021 and September 2023. A sample of 105 participants (7% of trial participants) was purposively selected to participate in three in-depth interviews at 2, 6, and 12 months during the trial. Another 111 (92 females and 19 males) participated in 14 focus group discussions across four sites. Data were analyzed thematically. Results: Repeated information sharing sessions facilitated by health workers helped participants understand key trial concepts and the design. Pre-exposure prophylaxis (PrEP) was widely recognised as a protective measure alongside experimental vaccines. While vaccines were preferred for convenience and minimal side effects, individual perceived HIV risk was a main motivation for adhering to PrEP. Supportive relationships with health workers and close family members encouraged engagement in the trial, including acceptance to use the products. However, misinformation and stigma in communities created barriers to participation, with some participants facing social harm. Conclusion: Overall, participants demonstrated a good understanding of randomisation, double-blinding, and placebo control, facilitated by clear, repeated communication from health workers. Strengthening strategies to enhance informed consent, reduce stigma, and promote trial acceptance is crucial for successful implementation and retention. Clinical trial registration: ClinicalTrials.gov NCT04066881. Registered on December 15, 2020.