HIV incidence after pre-exposure prophylaxis initiation among women and men at elevated HIV risk: A population-based study in rural Kenya and Uganda

Abstract

Background: Oral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP.

Methods and findings: During population-level HIV testing of individuals ≥15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning-based risk score, or self-identified HIV risk). We offered rapid or same-day PrEP initiation and flexible service delivery with follow-up visits at facilities or community-based sites at 4, 12, and every 12 weeks up to week 144. Among participants with incident HIV infection after PrEP initiation, we offered same-day antiretroviral therapy (ART) initiation and analyzed HIV RNA, tenofovir hair concentrations, drug resistance, and viral suppression (<1,000 c/ml based on available assays) after ART start. Using Poisson regression with cluster-robust standard errors, we compared HIV incidence among PrEP initiators to incidence among propensity score-matched recent historical controls (from the year before PrEP availability) in 8 of the 16 communities, adjusted for risk group. Among 74,541 individuals who tested negative for HIV, 15,632/74,541 (21%) were assessed to be at elevated HIV risk; 5,447/15,632 (35%) initiated PrEP (49% female; 29% 15-24 years; 19% in serodifferent partnerships), of whom 79% engaged in ≥1 follow-up visit and 61% self-reported PrEP adherence at ≥1 visit. Over 7,150 person-years of follow-up, HIV incidence was 0.35 per 100 person-years (95% confidence interval [CI] 0.22-0.49) among PrEP initiators. Among matched controls, HIV incidence was 0.92 per 100 person-years (95% CI 0.49-1.41), corresponding to 74% lower incidence among PrEP initiators compared to matched controls (adjusted incidence rate ratio [aIRR] 0.26, 95% CI 0.09-0.75; p = 0.013). Among women, HIV incidence was 76% lower among PrEP initiators versus matched controls (aIRR 0.24, 95% CI 0.07-0.79; p = 0.019); among men, HIV incidence was 40% lower, but not significantly so (aIRR 0.60, 95% CI 0.12-3.05; p = 0.54). Of 25 participants with incident HIV infection (68% women), 7/25 (28%) reported taking PrEP ≤30 days before HIV diagnosis, and 24/25 (96%) started ART. Of those with repeat HIV RNA after ART start, 18/19 (95%) had <1,000 c/ml. One participant with viral non-suppression was found to have transmitted viral resistance, as well as emtricitabine resistance possibly related to PrEP use. Limitations include the lack of contemporaneous controls to assess HIV incidence without PrEP and that plasma samples were not archived to assess for baseline acute infection.

Conclusions: Population-level offer of PrEP with rapid start and flexible service delivery was associated with 74% lower HIV incidence among PrEP initiators compared to matched recent controls prior to PrEP availability. HIV infections were significantly lower among women who started PrEP. Universal HIV testing with linkage to treatment and prevention, including PrEP, is a promising approach to accelerate reductions in new infections in generalized epidemic settings.

Trial registration: ClinicalTrials.gov NCT01864603.

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: CAK has received grant support to institution from the US National Institutes of Health and Gilead Research Scholars Program in HIV. DVH has received grant support from the US National Institutes of Health and study drug donation from Gilead Sciences. CM has received grant support from the US National Institutes of Health, the Stupski Foundation, and the Chan-Zuckerberg Biohub Foundation. LiBB has received grant support from the US National Institutes of Health. VJ has received grant support from the US Centers for Disease Control and Prevention/PEPFAR.

Figures

Fig 1. PrEP uptake following population-level HIV testing in 16 communities in rural Kenya and Uganda.

Individuals assessed to be at elevated risk of HIV acquisition (based on serodifferent partnership, HIV risk score, or otherwise self-identified HIV risk) were offered enhanced individual counseling on PrEP. Individuals neither in serodifferent partnerships nor identified by the risk score could self-identify as at risk of HIV acquisition. PrEP, pre-exposure prophylaxis.

Fig 2. Observed HIV incidence rate among PrEP initiators, overall and stratified by sex.

Observed HIV incidence rate per 100 person-years among PrEP initiators in all 16 study communities. CI, confidence interval; PrEP, pre-exposure prophylaxis; PY, person-years.

Fig 3. Observed HIV incidence rate among PrEP initiators compared to HIV incidence among recent matched controls prior to PrEP availability, overall and stratified by sex.

HIV incidence rate per 100 person-years in 8 study communities with propensity score–matched recent historical controls. CI, confidence interval; PrEP, pre-exposure prophylaxis.