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.

PrEP Use Among Female Sex Workers: No Evidence for Risk Compensation.

BACKGROUND: Little is known about risk compensation among female sex workers (FSW) on HIV pre-exposure prophylaxis (PrEP), and self-report of sexual behaviors is subject to bias. SETTING: Prospective observational PrEP demonstration study conducted among FSW in Cotonou, Benin. METHODS: Over a period of 24 months, we assessed and compared trends in unprotected sex as measured by self-report (last 2 or 14 days), by detection of sexually transmitted infections (STIs), and by vaginal detection of prostate-specific antigen and Y-chromosomal DNA, 2 biomarkers of semen exposure in the last 2 or 14 days, respectively. Trends were assessed and compared using a log-binomial regression that was simultaneously fit for all unprotected sex measures. RESULTS: Of 255 participants, 120 (47.1%) completed their follow-up. Prevalence of STI decreased from 15.8% (95% confidence interval: 11.8% to 21.0%) at baseline to 2.1% (95% confidence interval: 0.4% to 10.2%) at 24 months of follow-up (P-trend = 0.04). However, we observed no trend in self-report of unprotected sex in the last 2 (P = 0.42) or 14 days (P = 0.49), nor in prostate-specific antigen (P = 0.53) or Y chromosomal DNA (P = 0.25) over the same period. We observed no statistically significant difference between trends in self-report of unprotected sex and trends in biomarkers of semen exposure in the last 2 days (P = 0.14) or in the last 14 days (P = 0.29). CONCLUSIONS: We observed no evidence of risk compensation, and a decrease in STI among FSW on PrEP. PrEP intervention may be an opportunity to control STI among FSW. Future studies should assess risk compensation with biomarkers of semen exposure when possible.

Biological Validation of Self-Reported Unprotected Sex and Comparison of Underreporting Over Two Different Recall Periods Among Female Sex Workers in Benin.

BACKGROUND: Self-reported unprotected sex validity is questionable and is thought to decline with longer recall periods. We used biomarkers of semen to validate self-reported unprotected sex and to compare underreporting of unprotected sex between 2 recall periods among female sex workers (FSW). METHODS: At baseline of an early antiretroviral therapy and pre-exposure prophylaxis demonstration study conducted among FSW in Cotonou, Benin, unprotected sex was assessed with retrospective questionnaires, and with vaginal detection of prostate-specific antigen (PSA) and Y-chromosomal deoxyribonucleic acid (Yc-DNA). Underreporting in the last 2 or 14 days was defined as having reported no unprotected sex in the recall period while testing positive for PSA or Yc-DNA, respectively. Log-binomial regression was used to compare underreporting over the 2 recall periods. RESULTS: Unprotected sex prevalence among 334 participants was 25.8% (50.3%) according to self-report in the last 2 (or 14) days, 32.0% according to PSA, and 44.3% according to Yc-DNA. The proportion of participants underreporting unprotected sex was similar when considering the last 2 (18.9%) or 14 days (21.0%; proportion ratio = 0.90; 95% confidence interval, 0.72-1.13). Among the 107 participants who tested positive for PSA, 19 (17.8%) tested negative for Yc-DNA. CONCLUSIONS: Underreporting of unprotected sex was high among FSW but did not seem to be influenced by the recall period length. Reasons for discrepancies between PSA and Yc-DNA detection, where women tested positive for PSA but negative for Yc-DNA, should be further investigated.

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.

Violence, condom breakage, and HIV infection among female sex workers in Benin, West Africa.

OBJECTIVE: To examine the relationship between violence, condom breakage, and HIV prevalence among female sex workers (FSWs). METHODS: Data were obtained from the 2012 cross-sectional integrated biological and behavioral survey conducted in Benin. Multivariable log-binomial regression was used to estimate the adjusted prevalence ratios of HIV infection and condom breakage in relation to violence toward FSWs. A score was created to examine the relationship between the number of violence types reported and HIV infection. RESULTS: Among the 981 women who provided a blood sample, HIV prevalence was 20.4%. During the last month, 17.2%, 13.5%, and 33.5% of them had experienced physical, sexual, and psychological violence, respectively. In addition, 15.9% reported at least 1 condom breakage during the previous week. There was a significant association between all types of violence and HIV prevalence. The adjusted prevalence ratios of HIV were 1.45 (95% confidence interval [95% CI], 1.05-2.00), 1.42 (95% CI, 1.02-1.98), and 1.41 (95% CI, 1.08-1.41) among those who had ever experienced physical, sexual, and psychological violence, respectively. HIV prevalence increased with the violence score (P = 0.002, test for trend), and physical and sexual violence were independently associated with condom breakage (P = 0.010 and P = 0.003, respectively). CONCLUSIONS: The results show that violence is associated with a higher HIV prevalence among FSWs and that condom breakage is a potential mediator for this association. Longitudinal studies designed to analyze this relationship and specific interventions integrated to current HIV prevention strategies are needed to reduce the burden of violence among FSWs.

Disease patterns and causes of death of hospitalized HIV-positive adults in West Africa: a multicountry survey in the antiretroviral treatment era.

OBJECTIVE: We aimed to describe the morbidity and mortality patterns in HIV-positive adults hospitalized in West Africa. METHOD: We conducted a six-month prospective multicentre survey within the IeDEA West Africa collaboration in six adult medical wards of teaching hospitals in Abidjan, Ouagadougou, Cotonou, Dakar and Bamako. From April to October 2010, all newly hospitalized HIV-positive patients were eligible. Baseline and follow-up information until hospital discharge was recorded using standardized forms. Diagnoses were reviewed by a local event validation committee using reference definitions. Factors associated with in-hospital mortality were studied with a logistic regression model. RESULTS: Among 823 hospitalized HIV-positive adults (median age 40 years, 58% women), 24% discovered their HIV infection during the hospitalization, median CD4 count was 75/mm(3) (IQR: 25-177) and 48% had previously received antiretroviral treatment (ART). The underlying causes of hospitalization were AIDS-defining conditions (54%), other infections (32%), other diseases (8%) and non-specific illness (6%). The most frequent diseases diagnosed were: tuberculosis (29%), pneumonia (15%), malaria (10%) and cerebral toxoplasmosis (10%). Overall, 315 (38%) patients died during hospitalization and the underlying cause of death was AIDS (63%), non-AIDS-defining infections (26%), other diseases (7%) and non-specific illness or unknown cause (4%). Among them, the most frequent fatal diseases were: tuberculosis (36%), cerebral toxoplasmosis (10%), cryptococcosis (9%) and sepsis (7%). Older age, clinical WHO stage 3 and 4, low CD4 count, and AIDS-defining infectious diagnoses were associated with hospital fatality. CONCLUSIONS: AIDS-defining conditions, primarily tuberculosis, and bacterial infections were the most frequent causes of hospitalization in HIV-positive adults in West Africa and resulted in high in-hospital fatality. Sustained efforts are needed to integrate care of these disease conditions and optimize earlier diagnosis of HIV infection and initiation of ART.

Sexual behaviour after antiretroviral therapy initiation in female sex workers and HIV-positive patients from the general population, Cotonou, Benin.

From September 2008 to December 2011, we enrolled and followed-up 247 HIV-negative, 88 untreated and 32 treated HIV-positive female sex workers (FSWs), as well as 238 untreated and 115 treated HIV-positive patients from the general population (GP) of Cotonou, Benin. We wanted to assess the effect of antiretroviral therapy (ART) on sexual risk-taking in FSWs and patients from the GP. We used multivariate log binomial regression models for repeated measures to compare risky behaviours reported during pre-ART and post-ART visits and we performed linear time-trend analyses to assess changes in condom use in all five groups. At 58.8% of pre-ART and 45.3% of post-ART visits (adjusted p-value=0.293), treated FSWs have reported ≥16 clients during the last week of work. Inconsistent condom use with clients over the same period decreased by more than 50% (from 20.7 to 10.0%, adjusted p-value=0.082). In treated patients from the GP, inconsistent condom use with regular partners during the last four months was reported at 52.8% of pre-ART and 53.5% of post-ART visits (p=0.778). Reported casual sex was stable (36.8% versus 38.7%, adjusted p-value=0.924). In linear time-trend analyses, there was a significant downward trend in inconsistent condom use at the early stage of the study and stability thereafter in all HIV-negative and HIV-positive FSWs. There was no negative alteration in sexual behaviour following ART initiation either inpatients from the GP or in FSWs. The results underscore the key role of concomitant sexual risk-reduction strategies.

Decline in the prevalence of HIV and sexually transmitted infections among female sex workers in Benin over 15 years of targeted interventions.

BACKGROUND: An HIV-preventive intervention targeting the sex work milieu and involving fully integrated components of structural interventions, communication for behavioral change and care for sexually transmitted infections (STIs), was implemented in Benin by a Canadian project from 1992 to 2006. It first covered Cotonou before being extended to other main cities from 2000. At the project end, the Beninese authorities took over the intervention, but structural interventions were interrupted and other intervention components were implemented separately. We estimated time trends in HIV/STI prevalence among female sex workers (FSWs) from 1993 to 2008 and assessed the impact of the change in intervention model on trends. METHODS: Six integrated biological and behavioral surveys were carried out among FSWs. Time trend analysis controlled for potential sociodemographic confounders using log-binomial regression. RESULTS: In Cotonou, from 1993 to 2008, there was a significant decrease in HIV (53.3%-30.4%), gonorrhea (43.2%-6.4%), and chlamydia (9.4%-2.8%) prevalence (all adjusted P = 0.0001). The decrease in HIV and gonorrhea prevalence was also significant in the other cities between 2002 and 2008. In 2002, gonorrhea prevalence was lower in Cotonou than elsewhere (prevalence ratio = 0.53, 95% confidence interval: 0.32 to 0.88). From 2005 to 2008, there was an increase in gonorrhea prevalence (prevalence ratio = 1.76, 95% confidence interval: 1.17 to 2.65) in all cities combined. CONCLUSIONS: Our results suggest a significant impact of this targeted preventive intervention on HIV/STI prevalence among FSWs. The recent increase in gonorrhea prevalence could be related to the lack of integration of the intervention components.

Naturally-occurring genetic variants in human DC-SIGN increase HIV-1 capture, cell-transfer and risk of mother-to-child transmission.

BACKGROUND: Mother-to-child transmission (MTCT) is the main cause of HIV-1 infection in children worldwide. Dendritic cell-specific ICAM-3 grabbing-nonintegrin (DC-SIGN, also known as CD209) is an HIV-1 receptor that enhances its transmission to T cells and is expressed on placental macrophages. METHODS AND FINDINGS: We have investigated the association between DC-SIGN genetic variants and risk of MTCT of HIV-1 among Zimbabwean infants and characterized the impact of the associated mutations on DC-SIGN expression and interaction with HIV-1. DC-SIGN promoter (p-336C and p-201A) and exon 4 (198Q and 242V) variants were all significantly associated with increased risk of intrauterine (IU) HIV-1 infection. Promoter variants decreased DC-SIGN expression both in vitro and in placental CD163(+) macrophages (Hofbauer cells) of HIV-1 unexposed infants but not of HIV-1 exposed infants. The exon 4 protein-modifying mutations increased HIV-1 capture and transmission to T cells in vitro. CONCLUSION: This study provides compelling evidence to support an important role of DC-SIGN in IU HIV-1 infection.