Prevalence of pretreatment HIV resistance to integrase inhibitors in West African and Southeast Asian countries.

OBJECTIVES: Integrase strand transfer inhibitors (INSTIs) have been recently recommended as the preferred first-line option for antiretroviral treatment initiators in low- and middle-income countries (LMICs) in response to the growing circulation of resistant HIV to non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we estimated the frequency of pretreatment drug resistance (PDR) to INSTIs in West Africa and Southeast Asia. MATERIALS AND METHODS: Using samples collected from 2015 to 2016, and previously used to assessed PI, NRTI and NNRTI resistance, we generated HIV integrase sequences and identified relevant INSTI PDR mutations using the Stanford and ANRS algorithms. RESULTS: We generated 353 integrase sequences. INSTI PDR frequency was low, 1.1% (4/353) overall, ranging from 0% to 6.3% according to country. However, frequency of PDR to any drug class was very high, 17.9% (95% CI: 13.9%-22.3%), and mostly associated with a high level of NNRTI PDR, 9.7%, and a moderate level of NRTI PDR, 5.3%. CONCLUSIONS: Our results support the recent introduction of INSTIs in LMICs to improve treatment outcome in these settings, but also stress the need for effective actions to prevent uncontrolled emergence of drug resistance to this drug class.

Mathematical Model Impact Analysis of a Real-Life Pre-exposure Prophylaxis and Treatment-As-Prevention Study Among Female Sex Workers in Cotonou, Benin.

BACKGROUND: Daily pre-exposure prophylaxis (PrEP) and treatment-as-prevention (TasP) reduce HIV acquisition and transmission risk, respectively. A demonstration study (2015-2017) assessed TasP and PrEP feasibility among female sex workers (FSW) in Cotonou, Benin. SETTING: Cotonou, Benin. METHODS: We developed a compartmental HIV transmission model featuring PrEP and antiretroviral therapy (ART) among the high-risk (FSW and clients) and low-risk populations, calibrated to historical epidemiological and demonstration study data, reflecting observed lower PrEP uptake, adherence and retention compared with TasP. We estimated the population-level impact of the 2-year study and several 20-year intervention scenarios, varying coverage and adherence independently and together. We report the percentage [median, 2.5th-97.5th percentile uncertainty interval (95% UI)] of HIV infections prevented comparing the intervention and counterfactual (2017 coverages: 0% PrEP and 49% ART) scenarios. RESULTS: The 2-year study (2017 coverages: 9% PrEP and 83% ART) prevented an estimated 8% (95% UI 6-12) and 6% (3-10) infections among FSW over 2 and 20 years, respectively, compared with 7% (3-11) and 5% (2-9) overall. The PrEP and TasP arms prevented 0.4% (0.2-0.8) and 4.6% (2.2-8.7) infections overall over 20 years, respectively. Twenty-year PrEP and TasP scale-ups (2035 coverages: 47% PrEP and 88% ART) prevented 21% (17-26) and 17% (10-27) infections among FSW, respectively, and 5% (3-10) and 17% (10-27) overall. Compared with TasP scale-up alone, PrEP and TasP combined scale-up prevented 1.9× and 1.2× more infections among FSW and overall, respectively. CONCLUSIONS: The demonstration study impact was modest, and mostly from TasP. Increasing PrEP adherence and coverage improves impact substantially among FSW, but little overall. We recommend TasP in prevention packages.

Early antiretroviral therapy and daily pre-exposure prophylaxis for HIV prevention among female sex workers in Cotonou, Benin: a prospective observational demonstration study.

INTRODUCTION: In sub-Saharan Africa, HIV prevalence remains high, especially among key populations. In such situations, combination prevention including clinical, behavioural, structural and biological components, as well as adequate treatment are important. We conducted a demonstration project at the Dispensaire IST, a clinic dedicated to female sex workers (FSWs) in Cotonou, on early antiretroviral therapy (E-ART, or immediate "test-and-treat") and pre-exposure prophylaxis (PrEP). We present key indicators such as uptake, retention and adherence. METHODS: In this prospective observational study, we recruited FSWs from October 4th 2014 to December 31st 2015 and followed them until December 31st 2016. FSWs were provided with daily tenofovir disoproxil fumarate/emtricitabine (Truvada® ) for PrEP or received a first-line antiretroviral regimen as per Benin guidelines. We used generalized estimating equations to assess trends in adherence and sexual behaviour. RESULTS: Among FSWs in the catchment area, HIV testing coverage within the study framework was 95.5% (422/442). At baseline, HIV prevalence was 26.3% (111/422). Among eligible FSWs, 95.5% (105/110) were recruited for E-ART and 88.3% (256/290) for PrEP. Overall retention at the end of the study was 59.0% (62/105) for E-ART and 47.3% (121/256) for PrEP. Mean (±SD) duration of follow-up was 13.4 (±7.9) months for E-ART and 11.8 (±7.9) months for PrEP. Self-reported adherence was over 90% among most E-ART participants. For PrEP, adherence was lower and the proportion with 100% adherence decreased over time from 78.4% to 56.7% (p-trend < 0.0001). During the 250.1 person-years of follow-up among PrEP initiators, two seroconversions occurred (incidence 0.8/100 person-years (95% confidence interval: 0.3 to 1.9/100 person-years)). The two seroconverters had stopped using PrEP for at least six months before being found HIV-infected. In both groups, there was no evidence of reduced condom use. CONCLUSIONS: This study provides data on key indicators for the integration of E-ART and PrEP into the HIV prevention combination package already offered to FSWs in Benin. PrEP may be more useful as an individual intervention for adherent FSWs rather than a specific public health intervention. E-ART was a more successful intervention in terms of retention and adherence and is now offered to all key populations in Benin. STUDY REGISTRATION: ClinicalTrials.gov NCT02237.