Evaluating adaptive HIV pre-exposure prophylaxis adherence interventions for young South African women: results from a sequential multiple assignment randomized trial


BACKGROUND: Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy for adolescent girls and young women (AGYW). Widespread PrEP delivery will require identification of layered support strategies for AGYW with diverse needs. We conducted the first sequential multiple assignment randomized trial (SMART) to evaluate stepped PrEP adherence support interventions for AGYW in South Africa.
METHODS: 'PrEP SMART' was conducted in Johannesburg from 2019'2022. Sexually active, HIV-negative women ages 18'25 years were offered PrEP and randomized to receive standard PrEP counseling with either weekly two-way SMS or WhatsApp support. Those with low PrEP adherence through Month 2 ('non-responders') were re-randomized to quarterly visits with drug-level feedback (DLFB) or monthly visits with issue-focused counseling. The primary outcome was high adherence (tenofovir diphosphate [TFV-DP] '¥700 fmol/punch) from dried blood spots (DBS) at Month 9. We assessed the effects of the initial interventions on TFV-DP at Month 9, the effects of the intensified interventions among non-responders, and the optimal intervention sequence.
RESULTS: Of 360 AGYW, the median age was 21, 31.4% had sexually transmitted infections at enrollment, and 77.5% were retained through Month 9 despite COVID-19 disruptions. Of those with DBS, 58.6% (N=164) had TFV-DP '¥700 fmol/punch at Month 2 and 24.7% (N=66) at Month 9. At Month 9, 34/133 (25.6%) AGYW in the two-way SMS arm and 32/134 (23.9%) in the WhatsApp arm had high PrEP adherence (relative risk [RR]=1.07; 95% confidence interval [95% CI]=0.70'1.63; p=0.75). Among non-responders, 4/49 (8.2%) in the DLFB arm and 3/51 (5.9%) in the monthly counseling arm had high adherence at Month 9 (RR=1.39; 95% CI=0.33'5.88; p=0.66). Across the four dynamic treatment strategies, the estimated probability of high adherence at Month 9 was 23'27% (p=0.94).
CONCLUSIONS: In this study, PrEP adherence was higher than in comparable cohorts, despite the COVID-19 pandemic. Re-engaging non-responders after two months was challenging; individual-level interventions may not overcome structural PrEP barriers suggesting that longer-acting PrEP formulations may benefit this population. Our data show that individual tailored adherence approaches (SMS, WhatsApp) have similar impact on PrEP adherence and PrEP programs can adopt approaches based on likelihood of scalability.