PrEP uptake, persistence, adherence, and effect of retrospective drug level feedback on PrEP adherence among young women in southern Africa: Results from HPTN 082, a randomized controlled trial

Abstract

Background Pre-exposure prophylaxis (PrEP) is highly effective and an important prevention tool for African adolescent girls and young women (AGYW), but adherence and persistence are challenging. PrEP adherence support strategies for African AGYW were studied in an implementation study. Methods and findings HIV Prevention Trials Network (HPTN) 082 was conducted in Cape Town, Johannesburg (South Africa) and Harare (Zimbabwe) from October 2016 to October 2018 to evaluate PrEP uptake, persistence, and the effect of drug level feedback on adherence. Sexually active HIV–negative women ages 16–25 were offered PrEP and followed for 12 months; women who accepted were randomized to standard adherence support (counseling, 2-way SMS, and adherence clubs) or enhanced adherence support with adherence feedback from intracellular tenofovir-diphosphate (TFV-DP) levels in dried blood spots (DBS). PrEP uptake, persistence through 12 months (no PrEP hold or missed visits), and adherence were assessed. The primary outcome was high adherence (TFV-DP ≥700 fmol/punch) at 6 months, compared by study arm. Of 451 women enrolled, median age was 21 years, and 39% had curable sexually transmitted infections (STIs). Most (95%) started PrEP, of whom 55% had uninterrupted PrEP refills through 12 months. Of those with DBS, 84% had detectable TFV-DP levels at month 3, 57% at month 6, and 31% at month 12. At 6 months, 36/179 (21%) of AGYW in the enhanced arm had high adherence and 40/184 (22%) in the standard adherence support arm (adjusted odds ratio [OR] of 0.92; 95% confidence interval [CI] 0.55, 1.34; p = 0.76). Four women acquired HIV (incidence 1.0/100 person-years), with low or undetectable TFV-DP levels at or prior to seroconversion, and none of whom had tenofovir or emtricitabine resistance mutations. The study had limited power to detect a modest effect of incentives on adherence, and there was limited awareness of PrEP at the time the study was conducted. Conclusions In this study, PrEP initiation was high, over half of study participants persisted with PrEP through month 12, and the majority of young African women had detectable TFV-DP levels through month 6 with one-fifth having high adherence. Drug level feedback in the first 3 months of PrEP use did not increase the proportion with high adherence at month 6. HIV incidence was 1% in this cohort with 39% prevalence of curable STIs and moderate PrEP adherence. Strategies to support PrEP use and less adherence-dependent formulations are needed for this population. Trial registration ClinicalTrials.gov NCT02732730.

Cross‐sectional trends in HIV prevalence among pregnant women in Botswana: an opportunity for PrEP?

“…The efficacy of PrEP in men who have sex with men is well documented but studies among adolescents and resource‐limited settings have been less favourable [ 25 , 26 , 27 , 28 ]. Adherence and persistence have been identified as barriers among young women in sub‐Saharan Africa and both have significantly limited the potential impact of oral PrEP in this context [ 29 ]. However, second‐generation formulations of PrEP that are longer acting have demonstrated the ability to overcome these challenges [ 30 ].…”

HIV prevention: better choice for better coverage

“…While oral PrEP is highly suitable for some, there are a number of contexts in which daily, oral pills can become barriers to early use and persistence and may lead to pauses or even discontinuation [ 16 ]. Across studies in different populations and region, despite initial enthusiasm, there is evidence of inadequate daily PrEP adherence [ 17 ]. The SEARCH study in Uganda and Kenya highlighted difficulties among young women and young men, and this has been confirmed in other studies involving youth and adolescents [ 12 , 17 , 18 , 19 ].…”

“…Across studies in different populations and region, despite initial enthusiasm, there is evidence of inadequate daily PrEP adherence [ 17 ]. The SEARCH study in Uganda and Kenya highlighted difficulties among young women and young men, and this has been confirmed in other studies involving youth and adolescents [ 12 , 17 , 18 , 19 ].…”

Adaptive HIV pre-exposure prophylaxis adherence interventions for young South African women: Study protocol for a sequential multiple assignment randomized trial

“…However, despite promising PrEP initiation rates (with 95–100% of those screened and eligible for PrEP initiating PrEP), PrEP adherence and continuation during periods of HIV risk remain a challenge for some AGYW with retention rates around 50% by Month 12 and 15% by Month 24 [ 21 ]. In PrEP demonstration projects and delivery programs with AGYW, PrEP continuation rates declined to around 18–55% over the first six months and adherence was approximately 30% by 12 months [ 9 , 13 , 14 , 21 – 23 ], due to individual, interpersonal, and contextual factors, including lack of support, difficulty with habit formation, side effects, stigma related to PrEP and HIV, gender-based violence (GBV), and depression and stress [ 14 , 24 – 27 ]. Visit frequency and contact with providers may also be a factor; PrEP demonstration projects which explored the importance of visit frequency with young people found that PrEP adherence among South African AGYW generally declines as clinic visits move from monthly to quarterly [ 9 , 11 , 13 , 23 , 28 ].…”