Combined HIV Adolescent Prevention Study (CHAPS): comparison of HIV pre-exposure prophylaxis regimens for adolescents in sub-Saharan Africa-study protocol for a mixed-methods study including a randomised controlled trial

Abstract

Background: HIV remains a major public health issue, especially in Eastern and Southern Africa. Pre-exposure prophylaxis is highly effective when adhered to, but its effectiveness is limited by cost, user acceptability and uptake. The cost of a non-inferiority phase III trial is likely to be prohibitive, and thus, it is essential to select the best possible drug, dose and schedule in advance. The aim of this study, the Combined HIV Adolescent PrEP and Prevention Study (CHAPS), is to investigate the drug, dose and schedule of pre-exposure prophylaxis (PrEP) required for the protection against HIV and the acceptability of PrEP amongst young people in sub-Saharan Africa, and hence to inform the choice of intervention for future phase III PrEP studies and to improve strategies for PrEP implementation.

Methods: We propose a mixed-methods study amongst young people aged 13-24 years. The first component consists of qualitative research to identify the barriers and motivators towards the uptake of PrEP amongst young people in South Africa, Uganda and Zimbabwe. The second component is a randomised clinical trial (ClinicalTrials.gov NCT03986970, June 2019) using a novel ex vivo HIV challenge method to investigate the optimal PrEP treatment (FTC-TDF vs FTC-TAF), dose and schedule. We will recruit 144 amongst HIV-negative uncircumcised men aged 13-24 years from voluntary male medical circumcision clinics in two sites (South Africa and Uganda) and randomise them into one of nine arms. One group will receive no PrEP prior to surgery; the other arms will receive either FTC-TDF or FTC-TAF, over 1 or 2 days, and with the final dose given either 6 or 20 h prior to surgery. We will conduct an ex vivo HIV challenge on their resected foreskin tissue.

Discussion: This study will provide both qualitative and quantitative results to help decide the optimum drug, dose and schedule for a future phase III trial of PrEP. The study will also provide crucial information on successful strategies for providing PrEP to young people in sub-Saharan Africa.

Trial registration: ClinicalTrials.gov NCT03986970 . Registered on 14 June 2019.

Keywords: Adolescents; HIV; PrEP; South Africa; Uganda; Zimbabwe.

Fig. 1

Flow diagram of participant and foreskin journey for primary analysis (oral PrEP only). The numbers in the black boxes indicate the randomisation groups—there are nine, with each man allocated to exactly one group, with each group equally likely. This figure shows recruitment from both sites; recruitment will be split equally between SA (n = 72) and Uganda (n = 72). The numbers in the green boxes refer to the analysis groups. The main comparison will be between groups A–D. Group X, men who do not receive PrEP, will be used as a comparison and to ensure that the ex vivo challenge model is successful

Fig. 2

Flow diagram of participant and foreskin journey for oral PrEP, in vitro drug exposure and ex vivo HIV challenge. The analysis group identifiers in stage 2 comprise three components: a letter indicating the stage 1 group, a number (5 or 21) indicating the interval between the last oral PrEP dose and circumcision and an item indicating in vitro dosing (where 0 = no dose). The exceptions are the group of men who did not receive oral PrEP (Group X): these groups do not include the middle component

Fig. 3

SPIRIT figure. *p24 antigen ELISA was carried out until day 15 of culture