Human Immunodeficiency Virus Seroconversion Among Men Who Have Sex With Men Who Use Event-Driven or Daily Oral Pre-Exposure Prophylaxis (CohMSM-PrEP): A Multi-Country Demonstration Study From West Africa.

BACKGROUND: Data on human immunodeficiency virus (HIV) seroconversion among men who have sex with men (MSM) using pre-exposure prophylaxis (PrEP) in West Africa are needed. This study aimed to document HIV seroconversion and associated determinants, PrEP adherence, plasma drug concentrations, and HIV drug resistance in MSM using event-driven or daily PrEP in Burkina Faso, Côte d'Ivoire, Mali, and Togo. METHODS: A prospective cohort study was conducted in 2017-2021 among HIV-seronegative MSM aged 18 or over who were at high risk of HIV infection. Participants could choose between event-driven and daily PrEP, switch regimens, and discontinue or restart PrEP. The determinants of HIV incidence were investigated using a multivariate mixed-effects Poisson regression analysis. RESULTS: A total of 647 participants were followed for a total time of 1229.3 person-years. Of 5371 visits, event-driven PrEP was chosen in 3873 (72.1%), and daily PrEP in 1400 (26.1%). HIV incidence was 2.4 per 100 person-years (95% confidence interval [CI] 1.5-3.6) for event-driven PrEP, and 0.6 per 100 person-years (95% CI .1-2.3) for daily PrEP (adjusted incidence rate ratio 4.40, 95% CI 1.00-19.36, P = .050). Adequate adherence was lower with event-driven than daily PrEP (44.3% vs 74.9%, P < .001). Plasma drug concentrations were undetectable in 92 (97.9%) of the 94 measures taken for 23 participants who seroconverted. Only 1 participant had resistance to PrEP drugs. CONCLUSIONS: HIV seroconversions mainly occurred in participants who chose event-driven PrEP. The study's data highlighted major difficulties with adherence to this regimen. Improving adherence to event-driven PrEP constitutes a major research and public health priority in this context.

Decrease in incidence of sexually transmitted infections symptoms in men who have sex with men enrolled in a quarterly HIV prevention and care programme in West Africa (CohMSM ANRS 12324-Expertise France).

OBJECTIVE: Although men who have sex with men (MSM) are at high risk of STI, their access to tailored healthcare services remains limited in West Africa. We assessed the change in STI symptoms incidence over time among MSM enrolled in a quarterly HIV prevention and care programme in four cities in Burkina Faso, Côte d'Ivoire, Mali and Togo. METHODS: We performed a prospective cohort study in MSM followed up between 2015 and 2019. Men aged over 18 who reported anal sex with another man within the previous 3 months were offered quarterly syndromic diagnosis and treatment for STI, as well as HIV testing, peer-led counselling and support. Condoms and lubricants were also provided. The change in STI symptoms incidence during follow-up was investigated using a non-parametric trend test and mixed-effect Poisson regression models. RESULTS: 816 participants were followed for a total duration of 1479 person-years. 198 participants (24.3%) had at least one STI symptom during follow-up. Overall, STI symptoms incidence was 20.4 per 100 person-years (95% CI 18.4 to 22.6), ranging from 15.3 in Abidjan to 33.1 in Ouagadougou (adjusted incidence rate ratio (aIRR) 2.39, 95% CI 1.55 to 3.69, p<0.001). STI symptoms incidence was 16.8 and 23.0 per 100 person-years in HIV-positive and HIV-negative participants, respectively (aIRR 0.77, 95% CI 0.57 to 1.04, p=0.087). STI symptoms incidence decreased significantly from 29.9 per 100 person-years in the first 6 months to 8.6 at 30-35 months of follow-up (aIRR per 6-month increase 0.84, 95% CI 0.77 to 0.92, p<0.001). CONCLUSION: STI symptoms incidence decreased over time but the overall burden of STI appeared to be very high in MSM followed up in West Africa. STI services including counselling, diagnosis and treatment should be reinforced. Laboratory tests that allow accurate diagnosis of STI are required. Strengthening STI services will be critical for controlling the HIV and STI epidemics in this vulnerable population and in the general population. TRIAL REGISTRATION NUMBER: NCT02626286.

HIV pre-exposure prophylaxis for men who have sex with men in west Africa: a multicountry demonstration study.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) data in men who have sex with men (MSM) in west Africa are essential to guide its large-scale implementation. We assessed the uptake of event-driven and daily PrEP, HIV incidence, and changes over time in sexual behaviours and prevalence of bacterial sexually transmitted infections (STIs) in MSM in Burkina Faso, Côte d'Ivoire, Mali, and Togo. METHODS: We did a prospective cohort study from Nov 20, 2017, to April 14, 2020, in four community-based clinics in Abidjan (Côte d'Ivoire), Bamako (Mali), Lomé (Togo), and Ouagadougou (Burkina Faso). Participants were MSM aged 18 years or older at substantial risk of HIV infection. Participants could choose between event-driven (2+1+1 dosing) and daily oral PrEP (tenofovir disoproxil fumarate 300 mg plus emtricitabine 200 mg), switch regimen, and discontinue or restart PrEP. We compared HIV incidence in this study with that of the same cohort before the availability of PrEP (CohMSM). Statistical analysis included the Kaplan-Meier method and mixed-effects regression models. This study is registered with ClinicalTrials.gov, NCT03459157. FINDINGS: We followed up 598 participants for a total of 743·6 person-years. At enrolment, 445 (74%) of 598 participants chose event-driven PrEP and 153 (26%) of 598 chose daily PrEP. 60 (13%) of 445 and 65 (42%) of 153 participants switched PrEP regimen at least once (p<0·0001). 159 participants (27%) were lost to follow-up. Overall HIV incidence was 2·3 per 100 person-years (95% CI 1·3-3·7; adjusted incidence rate ratio 0·21, 95% CI 0·12-0·36 compared with CohMSM). Adherence was optimal in 802 (41%) of 1946 measures with event-driven PrEP and in 394 (71%) of 554 measures with daily PrEP (p<0·0001). Coverage of sex acts with PrEP only and PrEP and condom decreased during follow-up (p=0·039 if PrEP only; p=0·0025 if PrEP and condom). The frequency of condomless anal sex remained stable (p=0·96). The number of male sexual partners (p<0·0001) and number of sex acts with casual male partners (p=0·0014 for 1-4 sex acts in previous 4 weeks; p=0·030 for ≥5 sex acts) decreased. The prevalence of gonorrhoea, chlamydia, and syphilis remained stable. INTERPRETATION: PrEP availability helped prevent HIV infection and did not lead to an increase in risky sexual behaviours or other STIs. PrEP should be urgently implemented in west Africa. Retention in care and PrEP adherence require special attention to ensure PrEP reaches its full prevention potential. FUNDING: ANRS and Expertise France. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Adherence to quarterly HIV prevention services and its impact on HIV incidence in men who have sex with men in West Africa (CohMSM ANRS 12324 - Expertise France).

BACKGROUND: Access to tailored HIV prevention services remains limited for West African MSM. We assessed adherence to quarterly HIV prevention services and its impact on HIV incidence in MSM followed up in four cities in Burkina Faso, Côte d'Ivoire, Mali, and Togo. METHODS: We performed a prospective cohort study between 2015 and 2018. HIV-negative MSM aged over 18 benefited from quarterly medical visits which included a clinical examination, HIV testing, screening and treatment for other sexually transmitted infections, peer-led counselling and support, and the provision of condoms and lubricants. Determinants of adherence to quarterly follow-up visits and incident HIV infections were identified using generalized estimating equation models and Cox proportional hazard models, respectively. RESULTS: 618 MSM were followed up for a median time of 20.0 months (interquartile range 15.2-26.3). Overall adherence to quarterly follow-up visits was 76.5% (95% confidence interval [CI] 75.1-77.8), ranging from 66.8% in Abidjan to 87.3% in Lomé (p < 0.001). 78 incident HIV infections occurred during a total follow-up time of 780.8 person-years, giving an overall incidence of 10.0 per 100 person-years (95% CI 8.0-12.5). Adherence to quarterly follow-up visits was not associated with the risk of incident HIV infection (adjusted hazard ratio 0.80, 95% CI 0.44-1.44, p = 0.545). CONCLUSIONS: Strengthening HIV prevention services among MSM in West Africa, including the use of PrEP, will be critical for controlling the epidemic, not only in this key population but also in the general population. Quarterly follow-up of MSM, which is essential for PrEP delivery, appears feasible. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02626286 (December 10, 2015).

Heterogeneity in the Prevalence of High-Risk Human Papillomavirus Infection in Human Immunodeficiency Virus-Negative and Human Immunodeficiency Virus-Positive Men Who Have Sex With Men in West Africa.

BACKGROUND: Men who have sex with men (MSM) are at high risk of human papillomavirus (HPV) infection. We assessed (i) the prevalence of high-risk HPV (HR-HPV) infection and associated factors, and (ii) the prevalence of vaccine-preventable HPV infections in MSM in Burkina Faso, Côte d'Ivoire, Mali, and Togo. METHODS: A cross-sectional study was conducted in 2017-2018 among MSM ≥18 years old followed in community-based clinics. HPV infection was investigated in oral and anal samples using the e-BRID system. Factors associated with HR-HPV infection were identified using multivariate logistic regressions. RESULTS: Among 631 participants, 425 were HIV-negative and 206 HIV-positive. HR-HPV prevalence ranged from 9.2% to 34.8% in the former, and 33.3% to 71.0% in the latter, according to the study country. In multivariate analysis, HIV infection (adjusted odds ratio (aOR) 3.61, 95% confidence interval (CI) 2.48-5.27) and study country (4.73, 2.66-8.43 for Mali; 3.12, 1.68-5.80 for Burkina Faso; 3.51, 1.92-6.42 for Togo) were associated with HR-HPV infection. Other associated factors were low educational level, self-defined homosexual identity, and condomless anal sex. The prevalence of infections which can be prevented with bivalent, quadrivalent, and nonavalent vaccines was 5.9, 27.1, and 34.6% in HIV-negative participants, and 18.9, 43.7, and 54.9% in HIV-positive participants, respectively. CONCLUSIONS: HR-HPV prevalence was very heterogeneous between the study countries in both HIV-negative and HIV-positive MSM. Vaccine-preventable HPV infections predominated. Vaccination should be proposed to young MSM to reduce the burden of HPV infection in this vulnerable population and their female partners in West Africa.

Assessment of mental health outcomes and associated factors among workers in community-based HIV care centers in the early stage of the COVID-19 outbreak in Mali.

BACKGROUND AND OBJECTIVES: In Mali, the non-governmental association (NGO) ARCAD Santé PLUS launched the CovidPrev program in response to the COVID-19 outbreak to ensure continuity of HIV care-related activities. This study aimed to identify individual and structural factors associated with mental health disorders (MHD) in the NGO's healthcare workers (HCW) in the early stage of the outbreak. METHODS: Data were collected between April 6 and 11, 2020 for 135 HCW in ARCAD Santé PLUS's 18 community-based HIV care centers. Outcomes corresponded to the PHQ-9, GAD-7 and ISI instruments for depression, anxiety and insomnia, respectively. A general mixture model with a negative binomial distribution was implemented. RESULTS: Most HCW were men (60.7%) and median age was 40 years IQR[33-46]. Symptoms of depression, anxiety and insomnia were declared by 71.9, 73.3, and 77% participants, respectively. Women were at greater risk of MHD. A lack of personal protection equipment and human resources, especially nurses, was associated with a high risk of MHD. CONCLUSIONS: Health policy must place non-front line HCW, including those in NGOs, at the core of the healthcare system response to the COVID-19 outbreak, as they ensure continuity of care for many diseases including HIV. The efficacy of public health strategies depends on the capacity of HCW to fully with and competently perform their duties.

Re-engagement in care of people living with HIV lost to follow-up after initiation of antiretroviral therapy in Mali: Who returns to care?

OBJECTIVES: We assessed cumulative incidence rates of and factors associated with re-engagement in HIV care for PLHIV lost to follow-up in Mali. METHODS: HIV-1-infected individuals lost to follow-up before 31/12/2013, ≥ 18 years old, who started ART from 2006 to 2012 at one of 16 care centres were considered. Loss to follow-up (LTFU) was defined as an interruption of ≥ 6 months during follow-up. The re-engagement in care in PLHIV lost to follow-up before 31/12/2013 was defined as having at least one clinical visit after LTFU. The cumulative incidence rates of re-engagement in care was estimated by Kaplan-Meier and its predictive factors were assessed using Cox models. Socio-demographic characteristics, clinical and immune status, period, region, centre expertise level, and distance from home at the start of ART plus a combined variable of duration of ART until LTFU and 12-month change in CD4 count were assessed. Multiple imputation was used to deal with missing data. RESULTS: We included 3,650 PLHIV lost to follow-up before December 2013, starting ART in nine outpatient clinics and seven hospitals (5+2 in Bamako and 4+5 in other regions): 35% male, median (IQR) age 35 (29-43), and duration of ART until LTFU 11 months (5-22). Among these PLHIV, 1,975 (54%) were definitively LTFU and 1,675 (46%) subsequently returned to care. The cumulative incidence rates of re-engagement in care rose from 39.0% at one year to 47.0% at three years after LTFU. Predictors of re-engagement in care were starting ART with WHO stage 1-2 and CD4 counts ≥ 200 cells/µL, being treated for ≥ 12 months with CD4 count gain ≥ 50 cells/µL, or being followed in Bamako. People followed at regional hospitals or outpatient clinics ≥ 5 km away, or being treated for ≥ 12 months with CD4 count gain < 50 cells/µL were less likely to return to care. CONCLUSIONS: Starting ART with a higher CD4 count, better gain in CD4 count, and being followed either in Bamako or close to home in the regions were associated with re-engagement in care.

Sex work among female workers in the traditional mining sector in Mali - results from the ANRS-12339 Sanu Gundo cross-sectional study in 2015.

Female sex workers (FSW) in mining sites are considered to be at very high risk of HIV infection. We aimed to characterize FSW at the Kôkôyô artisanal gold mining site in Mali, and identify factors associated with sex work using data from ANRS-12339 Sanu Gundo, a cross-sectional survey conducted in 2015 at the mine by ARCAD-SIDA, a Malian non-governmental organisation. People attending HIV-prevention activities were invited to participate in the quantitative and qualitative parts of the survey. A probit logistic regression was used for data analysis. Of 101 women who participated in the survey, 26.7% reported sex work as their main activity. Multivariate analysis showed that the probability of sex work as a main activity decreased by 1% per 1-year age increase (p = 0.020). Sex work was significantly more likely to be reported by single, divorced and widowed women (25.4% probability; p = 0.007). FSW were significantly more likely to be non-Malian (36.3% probability; p = 0.003), more likely to have a secondary activity (77% probability; p = 0.002), to work fewer than 56h/week (40.2% probability; p = 0.001) and to be in good health (12.1% probability; p = 0.016). In addition, being aware of the existence of sexually transmitted infection, using psychoactive substances, and having unprotected receptive anal sex during the previous six months were significantly associated with sex work (50.2%; p = 0.006; 45.6%, p = 0.003; and 7.4%, p = 0.016 probability, respectively). Qualitative findings confirm that poverty and boyfriends' refusal to use condoms remain key barriers to systematic condom use among FSW.

Impact of HIV-1 primary drug resistance on the efficacy of a first-line antiretroviral regimen in the blood of newly diagnosed individuals in Bamako, Mali.

Background: To achieve the 90-90-90 targets assigned by UNAIDS, it is crucial to monitor ART in HIV-1-infected patients, especially in resource-limited countries. Objectives: To evaluate the immunovirological response after 12 months of ART in newly HIV-1-diagnosed people in Bamako, Mali; to determine primary and acquired resistance rates to antiretroviral drugs; and to evaluate the impact of primary resistance on the efficacy of ART. Patients and methods: One hundred and nineteen HIV-1-infected people (88.2% women; median age 34 years) were enrolled between January and June 2014. HIV-1 RNA loads (Abbott RealTime HIV-1 assay) were tested in the blood before and at months 3, 6 and 12 after initiation of ART. Primary and acquired resistances to ART were evaluated by the Viroseq™ HIV-1 genotyping assay. Results: During the study, 8.4% of people died and 37% were lost to follow-up. After 1 year of ART, an undetectable HIV-1 RNA viral load was found in 87.7% of cases. The overall rate of primary drug resistance mutations was 17.5% (3.2%, 15.9% and 0% for NRTIs, NNRTIs and PIs, respectively). These mutations were not associated with either higher mortality rates or larger numbers of virological failures. The acquired resistance rate was estimated at 3.1%. Conclusions: Our study showed a high primary resistance level and a huge proportion of people non-adherent to the treatment programme. Reassuringly, almost 90% virological success and a low level of acquired mutations were observed in adherent people at month 12. Reinforced education, regular virological monitoring and early HIV-1 diagnosis may help to improve retention in the care system.

Prevalence of HIV at the Kokoyo informal gold mining site: what lies behind the glitter of gold with regard to HIV epidemics in Mali? A community-based approach (the ANRS-12339 Sanu Gundo cross-sectional survey).

OBJECTIVES: The aim of this article was to estimate HIV prevalence and the factors associated with HIV seropositivity in the population living and working at the informal artisanal small-scale gold mining (IASGM) site of Kokoyo in Mali, using data from the Sanu Gundo survey. Our main hypothesis was that HIV prevalence is higher in the context of IASGM than in the country as a whole. DESIGN: The ANRS-12339 Sanu Gundo was a cross-sectional survey conducted in December 2015. The quantitative survey consisted of face-to-face administration of questionnaires. Five focus groups were conducted for the qualitative survey. HIV prevalence was calculated for the sample, and according to the type of activity performed in IASGM. SETTINGS: The IASGM site of Kokoyo, one of the largest sites in Mali (between 6000 and 1000 people). PARTICIPANTS: 224 respondents: 37.5% were gold-diggers, 33% retail traders, 6.7% tombolomas (ie, traditional guards) and 9% female sex workers. The remaining 13.8% reported another activity (mainly street vending). PRIMARY AND SECONDARY OUTCOME MEASURES: HIV prevalence and HIV prevalence according to subgroup, as defined by their activity at the Kokoyo IASGM. A probit logistic regression was implemented to estimate the characteristics associated with HIV seropositivity. RESULTS: HIV prevalence for the total sample was 8% (95% CI 7.7% to 8.3%), which is much higher than the 2015 national prevalence of 1.3%Joint United Nations Programme on HIV/AIDS (UNAIDS). The probability of HIV seropositivity was 7.8% (p=0.037) higher for female non-sex workers than for any other category, and this probability increased significantly with age. Qualitative data revealed the non-systematic use of condoms with sex workers; and long distance from health services was the main barrier to accessing care. CONCLUSIONS: Integrated policymaking should pay special attention to infectious diseases among populations in IASGM zones. Bringing information/prevention activities closer to people working in gold mining zones is an urgent public health action.

Transmitted antiretroviral drug resistance in newly HIV-infected and untreated patients in Ségou and Bamako, Mali.

The WHO recommends regular surveillance for transmitted antiretroviral drug-resistant viruses in HIV antiretroviral treatment (ART)-naive patients in resource-limited settings. This study aimed to assess the prevalence of mutations associated with resistance in ART-naive patients newly diagnosed with HIV in Bamako and Ségou in Mali. HIV-positive patients who never received ART were recruited in Bamako and Ségou, Mali. The reverse transcriptase (RT) and protease (PR) genes of these patients were sequenced by the "ViroSeq" method. Analysis and interpretation of the resistance were made according to the WHO 2009 list of drug resistance mutations. In all, 51/54 (94.4%) sample patients were sequenced. The median age (IQR) of our patients was 24 (22-27) years and the median CD4 count was 380 (340-456) cells/mm(3). The predominant subtype was recombinant HIV-1 CRF02_AG (66.7%) followed by CRF06_cpx (12%) and CRF09_cpx (4%). Four patients had mutations associated with resistance, giving an overall prevalence of resistance estimated at 7.9%. There were two (4%) patients with nucleoside reverse transcriptase inhibitor (NRTI) mutations (one M184V and one T215Y), two (4%) with non-NRTI mutations (two K103N), and one (2%) with a protease inhibitor mutation (one I54V). The prevalence of primary resistance in newly infected patients in Mali is moderate (7.9%). This indicates that the standard NNRTI-based first-line regimen used in Mali is suboptimal for some patients. This study should be done regularly to inform clinical practice.

Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting.

OBJECTIVES: We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. METHODS: We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. RESULTS: Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm(3). Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). CONCLUSION: Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings.

Connection domain mutations during antiretroviral treatment failure in Mali: frequencies and impact on reverse transcriptase inhibitor activity.

Mutations in the connection domain (CD) of reverse transcriptase have been implicated in reverse transcriptase inhibitor (RTI) resistance, but this is controversial and little is known in non-B subtype HIV-1. We determined CD mutations prevalence in a population infected predominantly with CRF02_AG and investigated associations with phenotypic RTI resistance. Detected CD mutations were G335D (82.3%), A371V (69.8%), E399D (9.4%), N348I (5.2%), V365I (4.2), Y318F (2.1%), G333E (2.1%), and A360V (2.1%). Mutations were largely polymorphic and did not confer RTI resistance. The observed trend toward reduced likelihood of etravirine or nevirapine resistance in the presence of G335D should be investigated further.