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.