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.

Association of HIV Preexposure Prophylaxis Use With HIV Incidence Among Men Who Have Sex With Men in China

“…The observed outcome of D-PrEP use in our study was similar to that reported in randomized clinical trials 2,4 and was slightly higher than that in a demonstration project in Africa. 20 Consistent with previous open-label prospective cohorts, [8][9][10] the observed outcomes of D-PrEP and ED-PrEP use were similar. Incident HIV seroconversion among PrEP users could be explained by suboptimal adherence.…”

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

“…Further work in this cohort found higher adherence to PrEP was correlated with known risk factors for HIV, suggesting that women at higher risk might choose to accept and adhere to PrEP. 19 The SEARCH study 20 reported a decrease in HIV incidence of 74% in women who initiated PrEP. Conversely, in the recently completed vaccine trial HVTN 702, 21 PrEP was not provided on-site and few initiated PrEP; HIV incidence was 4·2 per 100 person-years, comparable to ECHO before the introduction of PrEP.…”

Introducing the Dapivirine Vaginal Ring in Sub-Saharan Africa: What Can We Learn from Oral PrEP?

“…With new data available that demonstrate population-level reductions in HIV incidence in the context of community-wide HIV testing and universal access to oral PrEP [ 24 •], a critical look at risk assessment is needed to inform delivery of oral PrEP and the DVR. The field has already started to evolve, with WHO and HIV prevention experts encouraging a reframing away from risk assessment toward an assessment of interest in and readiness for oral PrEP.…”

“…In some countries (e.g., South Africa and Namibia), oral PrEP could be delivered only by nurses who had undergone nurse-initiated management of antiretroviral therapy (NIMART) training. However, these approaches did not effectively reach general population groups at substantial risk of HIV, including AGYW, who are unlikely to seek out HIV-specific service delivery channels, have concerns about stigma, and prefer low-barrier models for preventive care (e.g., limited travel, short wait times) [ 19 •, 24 •, 41 ].…”