Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study

Abstract

Background As oral pre-exposure prophylaxis (PrEP) becomes the standard of prevention globally, its potential effect on HIV incidence in clinical trials of new prevention interventions is unknown, particularly for trials among women. In a trial measuring HIV incidence in African women, oral PrEP was incorporated into the standard of prevention in the trial's last year. We assessed the effect of on-site access to PrEP on HIV incidence in this natural experiment.Methods We did a nested interrupted time-series study using data from the ECHO trial. At 12 sites in four countries (Eswatini, Kenya, South Africa, and Zambia), women (aged 16-35 years) were randomly assigned to receive one of three contraceptives between Dec 14, 2015, and Sept 12, 2017, and followed up quarterly for up to 18 months to determine the effect of contraceptive method on HIV acquisition. Women were eligible if they wanted long-acting contraception, were medically qualified to receive study contraceptives, and had not used any of the study contraceptives in the past 6 months. The present analyses are limited to nine South African sites where on-site access to oral PrEP was implemented between March 13 and June 12, 2018. Using an interrupted time-series design, we compared HIV incidence before versus after PrEP access, limited to quarterly study visits at which on-site PrEP access was available to at least some participants and, in a sensitivity analysis, to the 180 days before and after access. The outcome was incident HIV infection, detected using two rapid HIV tests done in parallel for each participant at every scheduled follow-up visit. This study is registered on ClinicalTrials.gov, NCT02550067. Findings 2124 women were followed up after on-site PrEP access began, of whom 543 (26%) reported PrEP use. A total of 12 HIV seroconversions were observed in 556 person-years (incidence 2•16%) after on-site PrEP access, compared with 133 HIV seroconversions in 2860 person-years (4•65%) before PrEP access (adjusted incidence rate ratio [IRR] 0•45, 95% CI 0•25-0•82, p=0•0085). Similar results were also observed when limiting the analysis to 180 days before versus after PrEP access. A total of 46 HIV seroconversions were observed in 919 person-years within 180 days before PrEP access, compared with 11 seroconversions in 481 person-years in the 180 days following PrEP access (incidence 5•00 vs 2•29 per 100 person-years; IRR 0•43, 95% CI 0•22-0•88, p=0•012). Interpretation On-site access to PrEP as part of standard of prevention in a clinical trial among women in South Africa was associated with halving HIV incidence, when approximately a quarter of women started PrEP. Providing access to on-site PrEP could decrease incidence in HIV prevention trials. These data are also among the first to show in any setting that access to PrEP is associated with decreased HIV acquisition among South African women.

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial

“…10 Furthermore, HIV incidence in ECHO dropped by about 50% after on-site access to PrEP. 20 We found that 40% of women discontinued PrEP before the final visit in our study, and this was consistent with findings from a large systematic review and meta-analysis where about a third discontinued PrEP within the first month. 21 In our study and the VOICE trial, older age was associated with quantifiable tenofovir.…”

The case for prevention – Primary HIV prevention in the era of universal test and treat: A mathematical modeling study

“…Since the costs of these interventions are not all derived from the same study, the methodology of determining the unit costs of the different interventions in different countries may not be comparable. Oral PrEP costs may go down as implementation efficiencies are identified, and its cost-effectiveness will also increase if, as was demonstrated in the SEARCH and other studies, 31 , 47 , 48 , 49 users correctly identify periods when they are at higher risk and use the intervention during these periods. 50 Despite these limitations, the overall trends identified in this study of three sub-Saharan African countries with different epidemic characteristics should be applicable to other sub-Saharan African countries with generalized HIV epidemics.…”

The impact of prevention‐effective PrEP use on HIV incidence: a mathematical modelling study

“…Furthermore, HIV incidence in many PrEP implementation studies has been substantially lower than expected in the absence of PrEP despite a minority of participants adhering to PrEP. HIV incidence among all participants was 55% lower after PrEP became available during the Evidence for Contraceptive Options in HIV Outcomes (ECHO) trial in South Africa despite only 26% of participants reporting PrEP use [38]. In a study of young women in South Africa and Zimbabwe, only 21% of participants had high adherence (≥ 700 fmol/punch by dried blood spot) at 6 months after initiation.…”