Novel Cardiokine GDF3 Predicts Adverse Fibrotic Remodeling After Myocardial Infarction.

BACKGROUND: Myocardial infarction (MI) induces a repair response that ultimately generates a stable fibrotic scar. Although the scar prevents cardiac rupture, an excessive profibrotic response impairs optimal recovery by promoting the development of noncontractile fibrotic areas. The mechanisms that lead to cardiac fibrosis are diverse and incompletely characterized. We explored whether the expansion of cardiac fibroblasts after MI can be regulated through a paracrine action of cardiac stromal cells. METHODS: We performed a bioinformatic secretome analysis of cardiac stromal PW1+ cells isolated from normal and post-MI mouse hearts to identify novel secreted proteins. Functional assays were used to screen secreted proteins that promote fibroblast proliferation. The expressions of candidates were subsequently analyzed in mouse and human hearts and plasmas. The relationship between levels of circulating protein candidates and adverse post-MI cardiac remodeling was examined in a cohort of 80 patients with a first ST-segment-elevation MI and serial cardiac magnetic resonance imaging evaluations. RESULTS: Cardiac stromal PW1+ cells undergo a change in paracrine behavior after MI, and the conditioned media from these cells induced a significant increase in the proliferation of fibroblasts. We identified a total of 12 candidates as secreted proteins overexpressed by cardiac PW1+ cells after MI. Among these factors, GDF3 (growth differentiation factor 3), a member of the TGF-ß (transforming growth factor-ß) family, was markedly upregulated in the ischemic hearts. Conditioned media specifically enriched with GDF3 induced fibroblast proliferation at a high level by stimulation of activin-receptor-like kinases. In line with the secretory nature of this protein, we next found that GDF3 can be detected in mice and human plasma samples, with a significant increase in the days after MI. In humans, higher GDF3 circulating levels (measured in the plasma at day 4 after MI) were significantly associated with an increased risk of adverse remodeling 6 months after MI (adjusted odds ratio, 1.76 [1.03-3.00]; P=0.037), including lower left ventricular ejection fraction and a higher proportion of akinetic segments. CONCLUSIONS: Our findings define a mechanism for the profibrotic action of cardiac stromal cells through secreted cardiokines, such as GDF3, a candidate marker of adverse fibrotic remodeling after MI. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01113268.

Mobility and HIV vulnerabilities among female sex workers in Guinea-Bissau: findings from an integrated bio-behavioral survey.

BACKGROUND: Mobility is an important risk determinant for HIV given the potential for intermittent access to HIV services. Mobility may be particularly relevant among female sex workers, (FSW) who have been shown to be at high risk for HIV in settings around the world. Data regarding the role mobility plays in exacerbating HIV risks among FSW across Sub-Saharan Africa remains limited, and data on FSW in Guinea-Bissau is sparse. METHODS: FSW in four regions of Guinea-Bissau were recruited with a respondent-driven sampling (RDS) method and participated in an integrated bio-behavioral survey between September 27, 2017 and January 26, 2018. Associations between reported general mobility, mobility to or residence in Bissau, and social and HIV vulnerabilities among FSW in Guinea-Bissau were assessed using multivariable logistic regression models. Population proportions were weighted for RDS sampling, while logistic regression models were not. RESULTS: Survey respondents included 323 individuals in Bissau, 45 in Bissorã, 140 in Bafatá, and 59 in Gabu. Statistical analyses demonstrated that mobility to more than one destination was significantly associated with recent sex without a condom (ie, sex without a condom within the last three sex acts) with both clients (aOR: 2.47 (95% CI: 1.08, 5.64)) and non-paying partners (aOR: 5.39 (95% CI: 2.61, 11.15)) compared to non-mobility. However, mobility to one or more locations was also associated with higher odds of receiving HIV prevention information, and mobility to more than one location was associated with participating in programming with HIV-related organizations. CONCLUSIONS: These results suggest that while some prevention services including HIV prevention information reach mobile FSW in Guinea-Bissau more than their non-mobile counterparts, the higher rates of condomless sex among mobile FSW suggest that HIV prevention needs may remain unmet for mobile FSW in Guinea-Bissau. Additionally, the results suggest a nuanced relationship between mobility, place of residence, and HIV and social vulnerabilities and prevention indicators.

Characterizing Cross-Culturally Relevant Metrics of Stigma Among Men Who Have Sex With Men Across 8 Sub-Saharan African Countries and the United States.

Overcoming stigma affecting gay, bisexual, and other men who have sex with men (MSM) is a foundational element of an effective response to the human immunodeficiency virus (HIV) pandemic. Quantifying the impact of stigma mitigation interventions necessitates improved measurement of stigma for MSM around the world. In this study, we explored the underlying factor structure and psychometric properties of 13 sexual behavior stigma items among 10,396 MSM across 8 sub-Saharan African countries and the United States using cross-sectional data collected between 2012 and 2016. Exploratory factor analyses were used to examine the number and composition of underlying stigma factors. A 3-factor model was found to be an adequate fit in all countries (root mean square error of approximation = 0.02-0.05; comparative fit index/Tucker-Lewis index = 0.97-1.00/0.94-1.00; standardized root mean square residual = 0.04-0.08), consisting of "stigma from family and friends," "anticipated health-care stigma," and "general social stigma," with internal consistency estimates across countries of α = 0.36-0.80, α = 0.72-0.93, and α = 0.51-0.79, respectively. The 3-factor model of sexual behavior stigma cut across social contexts among MSM in the 9 countries. These findings indicate commonalities in sexual behavior stigma affecting MSM across sub-Saharan Africa and the United States, which can facilitate efforts to track progress on global stigma mitigation interventions.

Associations Between Economic Factors and Condom Use Behavior Among Female Sex Workers in Dakar and Mbour, Senegal.

Condom use remains a mainstay of HIV prevention programs around the world. However, data characterizing economic determinants of condom use among female sex workers (FSW) are limited, including in Senegal. We recruited 718 FSWs via respondent-driven sampling. Bivariate and multivariable regressions were conducted to assess the associations between economic variables and condom use at last sex. Paying rent (aRR: 1.07, 95%CI 1.01-1.13) was positively associated with condom use at last sex with new clients. No statistically significant associations were found between condom use and financial responsibility for dependent children, having additional source of income, sharing sex work earnings, or the ability to borrow from other FSWs, regardless of sexual partner types. The relationship between economic marginalization and consistent condom use among sex workers is complex reinforcing the need for behavioral economic research and prevention to be integrated into HIV prevention and treatment research and programs.

Accuracy of a multiparametric score based on pulse wave analysis for prediction of fluid responsiveness: ancillary analysis of an observational study.

PURPOSE: The pressure recording analytical method (PRAM) monitor is a non-invasive pulse contour cardiac output (CO) device that cannot be considered interchangeable with the gold standard for CO estimation. It, however, generates additional hemodynamic indices that need to be evaluated. Our objective was to investigate the performance of a multiparametric predictive score based on a combination of several parameters generated by the PRAM monitor to predict fluid responsiveness. METHODS: Secondary analysis of a prospective observational study from April 2016 to December 2017 in two French teaching hospitals. We included critically ill patients who were monitored by esophageal Doppler monitoring and an invasive arterial line, and received a 250-500 mL crystalloid fluid challenge. The main outcome measure was the predictive score discrimination evaluated by the area under the receiver operating characteristics curve. RESULTS: The three baseline PRAM-derived parameters associated with fluid responsiveness in univariate analysis were pulse pressure variation, cardiac cycle efficiency, and arterial elastance (P < 0.01, P = 0.03, and P < 0.01, respectively). The median [interquartile range] predictive score, calculated after discretization of these parameters according to their optimal threshold value was 3 [2-3] in fluid responders and 1 [1-2] in fluid non-responders, respectively (P < 0.001). The area under the curve of the predictive score was 0.807 (95% confidence interval, 0.662 to 0.909; P < 0.001). CONCLUSION: A multiparametric score combining three parameters generated by the PRAM monitor can predict fluid responsiveness with good positive and negative predictive values in intensive care unit patients.

RéSUMé: OBJECTIF: Le moniteur PRAM (pressure recording analytical method) est un dispositif non invasif de surveillance du débit cardiaque (DC) fondé sur la mesure de contour de l'onde de pouls qui ne peut être considéré comme interchangeable avec la référence de l'estimation du DC. Cependant, ce dispositif génère des indices hémodynamiques supplémentaires qui doivent être évalués. Notre objectif était d'examiner la performance d'un score prédictif multiparamétrique fondé sur une combinaison de plusieurs paramètres générés par le moniteur PRAM afin de prédire la réponse au remplissage volémique. MéTHODE: Analyse secondaire d'une étude observationnelle prospective entre avril 2016 et décembre 2017 dans deux hôpitaux universitaires français. Nous avons inclus des patients en état critique monitorés par un Doppler oesophagien et une ligne artérielle invasive, et ayant reçu un bolus de cristalloïdes de 250­500 mL. Le critère d'évaluation principal était la discrimination du score prédictif telle qu'évaluée par la surface sous la courbe de fonction d'efficacité de l'observateur (ROC). RéSULTATS: Les trois paramètres de base dérivés du PRAM associés à la réponse au remplissage dans l'analyse univariée étaient la variation de pression différentielle, l'efficacité du cycle cardiaque, et l'élastance artérielle (P < 0,01, P = 0,03, et P < 0,01, respectivement). Le score prédictif médian [écart interquartile], calculé après discrétisation de ces paramètres selon leur valeur seuil optimale, était de 3 [2­3] chez les répondeurs au remplissage et de 1 [1­2] chez les non-répondeurs, respectivement (P < 0,001). La surface sous la courbe du score prédictif était de 0,807 (intervalle de confiance 95 %, 0,662 à 0,909; P < 0,001). CONCLUSION: Un score multiparamétrique combinant trois paramètres générés par le moniteur PRAM peut prédire la réponse au remplissage volémique avec de bonnes valeurs prédictives positives et négatives chez les patients à l'unité de soins intensifs.

The relationship between depression and sexual health service utilization among men who have sex with men (MSM) in Côte d'Ivoire, West Africa.

BACKGROUND: In Cote D'Ivoire, there has been limited coverage of evidence-based sexual health services specifically supporting men who have sex with men (MSM). To date, there has been limited study of the determinants of engagement in these services including multiple intersecting stigmas and depression. METHODS: 1301 MSM aged 18 years and older, were recruited using respondent-driven sampling in Abidjan, Yamoussoukro, Gagnoa and Bouake, Cote d'Ivoire from January 2015 to October 2015. Inclusion criteria included anal sex with another man in the past 12 months were to complete a structured questionnaire including the Patient Health Questionnaire (PHQ)-9 to screen for depression. Chi-Square tests were used to test difference in healthcare utilization across variables, and multiple logistic regression was used to test the association between depression and health care utilization represented by HIV and sexually transmittable infection testing and treatment. RESULTS: Depression (aOR:1.40, 95% CI: 1.07-1.84), being aged 25-29 years (aOR:1.84, 95% CI: 1.11-3.03),unemployed (aOR:0.64, 95% CI: 0.42-0.98), being a student (aOR:0.67, 95% CI: 0.48-0.96), being identified as male (aOR:0.44, 95% CI: 0.29-0.67), and identifying as homosexual (aOR:0.74, 95% CI:0.56-0.99) were significantly associated with utilization of sexual health care services in the final multivariable model. Healthcare enacted stigma (aOR: 1.55, 95% CI: 1.03-2.33) was associated with utilizing sexual health care services, but perceived healthcare stigma, social stigma and family stigma were not. CONCLUSION: Given higher levels of depressive symptomatology among those engaging in sexual health care services, this engagement represents an opportunity for service integration which may have synergistic benefits for both sexual and mental health. Moreover, MSM in Cote D'Ivoire who had engaged in sexual health services were more likely to report having experienced health-care enacted stigma. Taken together, these results reinforce the need for stigma mitigation interventions to support sustained engagement in HIV prevention, treatment and care services as a means of reducing health disparities among MSM in Cote d'Ivoire.

Monitoring haemodynamic response to fluid-challenge in ICU: comparison of pressure recording analytical method and oesophageal Doppler: A prospective observational study.

BACKGROUND: The ability of the pressure recording analytical method (PRAM) in tracking change in cardiac output (ΔCO) after a fluid challenge in ICU needs to be evaluated with the most contemporary comparison methods recommended by experts. OBJECTIVE: Our objective was to report the trending ability of PRAM in tracking ΔCO after a fluid challenge in ICU and to compare this with oesophageal Doppler monitoring (ODM). DESIGN: Prospective, observational study. SETTING: Hôpital Lariboisière and Hôpital Européen George Pompidou, Paris, France, from April 2016 to December 2017. PATIENTS: Critically ill patients admitted to ICU with monitoring of CO monitored by ODM and invasive arterial pressure. INTERVENTION: ΔCO after fluid challenge was simultaneously registered with ODM and PRAM connected to the arterial line. MAIN OUTCOME MEASURE: Polar statistics (mean angular bias, radial limits of agreement and polar concordance rate) and clinical concordance evaluation (error grid and clinical concordance rate). Predictors of bias were determined. RESULTS: Sixty-eight fluid challenge were administered in 49 patients. At the time of fluid challenge, almost all were mechanically ventilated (99%), with 85% receiving norepinephrine. Admission diagnosis was septic shock in 70% of patients. Patients had a Sequential Organ Failure Assessment score of 10 [7 to 12] and a median Simplified Acute Physiology Score II of 61 [49 to 69]. Relative ΔCO bias was 7.8° (6.3°) with radial limits of agreement of ±41.7°, polar concordance rate 80% and clinical concordance rate 74%. ΔCO bias was associated with baseline bias (P = 0.007). Baseline bias was associated with radial location of the arterial line (P = 0.03). CONCLUSION: When compared with ODM, PRAM has insufficient performance to track ΔCO induced by fluid challenge in ICU patients. Baseline bias is an independent predictor of trending bias. TRIAL REGISTRATION: IRB 00010254-2016-033.

Sexual violence against female sex workers in The Gambia: a cross-sectional examination of the associations between victimization and reproductive, sexual and mental health.

BACKGROUND: Female sex workers (FSW) are a vulnerable population for sexual violence and poor sexual and reproductive health outcomes. Sexual violence against FSW has not been widely studied in The Gambia. This study will report the prevalence of and evaluate the health issues correlated with forced sex perpetrated by clients against FSW in The Gambia, and will secondly aim to inform future research and efforts to improve health outcomes for survivors of violence. METHODS: A cross-sectional survey was administered among 251 FSW accrued through a combination of chain referral and venue-based sampling in The Gambia. Eligibility criteria included being over 16 years old and having exchanged sex for money, goods, or favors in the past 12 months. RESULTS: There is a high prevalence of sexual violence against FSW in The Gambia, with 29% (n = 70) of participants reporting a client forced them to have sex in their lifetime. Women who reported forced sex by a client were more likely to report symptoms of depression (aOR 2.15, CI: 1.10-4.16 p < 0.05), unwanted pregnancy (aOR: 2.69, CI: 1.12-6.49 p < 0.05) and report "no", "difficult" or "somewhat difficult" access to condoms (aOR: 3.31, CI: 1.76-6.26 p < .01) compared to women who did not report forced sex. Client-perpetrated forced sex was also negatively associated with receiving any sexually transmitted infection (STI) test in the past 12 months (aOR: 0.49, CI: .26-.91 p < .05). CONCLUSION: FSW who experience sexual violence by a client are more likely to experience poor sexual, reproductive and mental health outcomes. Responding to sexual violence among FSW, including providing survivors with access to post-exposure prophylaxis, emergency contraception, and mental health services, must be a priority given the prevalence of forced sex and links with poor health outcomes. Efforts to reduce sexual violence against FSW is a vital strategy to improve the health and safety of FSW as well as impact the spread of HIV/STIs in The Gambia.

Mbaraan and the shifting political economy of sex in urban Senegal.

This paper examines transactional sex in Dakar as a window into broader processes of social and economic change in urban Senegal. Patterns of heterosexual behaviour in Senegal's capital (late and increasing age at first marriage for women, a relatively high divorce rate and a rise in transactional sex) reflect a confluence of socioeconomic forces that curtail some forms of heterosexual union and facilitate others. Our analysis focuses on the rise of mbaraan, a practice in which single, married and divorced women have multiple male partners. We argue that while mbaraan is in part an expression of women's agency and a transgression of dominant gender norms, it also reflects women's social and economic subordination and their inability to achieve self-sufficiency independent of men's financial support. We suggest that this urban phenomenon is the outcome of contradictory opportunities and constraints that women face as they grapple with material insecurity and marital disappointments.

Gay men and other men who have sex with men in West Africa: evidence from the field.

This paper presents a synthesis of lessons learned from field experiences in HIV prevention, treatment and care services for men who have sex with men in the four contiguous West African countries of the Gambia, Guinea-Bissau, Guinea-Conakry and Senegal. Service provision for men who have sex with men in these countries is contextualised by the epidemiology of HIV, as well as the socio-political environment. These countries share notable commonalities in terms of social structures and culture, though past approaches to the needs of men who have sex with men have varied greatly. This synthesis includes three distinct components. The first focuses on what is known about HIV epidemiology among men who have sex with men in these countries and provides an overview of the data gaps affecting the quality of service provision. The second aspect describes the HIV prevention and treatment services currently available and how organisations and strategies have evolved in their approach to working with men who have sex with men. Finally, an examination of the political and cultural climate highlights socio-cultural factors that enable or impede HIV prevention and treatment efforts for men who have sex with men. The review concludes with a series of recommendations for impactful research, advocacy and service provision to improve the health and human rights context for men who have sex with men in West Africa.

Association of Organizational Pathways With the Delay of Emergency Surgery.

Importance: Delayed admission of patients with surgical emergencies to the operating room occurs frequently and is associated with poor outcomes. In France, where 3 distinct organizational pathways in hospitals exist (a dedicated emergency operating room and team [DET], a dedicated operating room in a central operating theater [DOR], and no dedicated structure or team [NOR]), neither the incidence nor the influence of delayed urgent surgery is known, and no guidelines are available to date. Objective: To examine the overall frequency of delayed admission of patients with surgical emergencies to the operating room across the 3 organizational pathways in hospitals in France. Design, Setting, and Participants: This prospective multicenter cohort study was conducted in 10 French tertiary hospitals. All consecutive adult patients admitted for emergency surgery from October 5 to 16, 2020, were included and prospectively monitored. Patients requiring pediatric surgery, obstetrics, interventional radiology, or endoscopic procedures were excluded. Exposures: Emergency surgery. Main Outcomes and Measures: The main outcome was the global incidence of delayed emergency surgery across 3 predefined organizational pathways: DET, DOR, and NOR. The ratio between the actual time to surgery (observed duration between surgical indication and incision) and the ideal time to surgery (predefined optimal duration between surgical indication and incision according to the Non-Elective Surgery Triage classification) was calculated for each patient. Surgery was considered delayed when this ratio was greater than 1. Results: A total of 1149 patients were included (mean [SD] age, 55 [21] years; 685 [59.9%] males): 649 in the DET group, 320 in the DOR group, and 171 in the NOR group (missing data: n = 5). The global frequency of surgical delay was 32.5% (95% CI, 29.8%-35.3%) and varied across the 3 organizational pathways: DET, 28.4% (95% CI, 24.8%-31.9%); DOR, 32.2% (95% CI, 27.0%-37.4%); and NOR, 49.1% (95% CI, 41.6%-56.7%) (P < .001). The adjusted odds ratio for delay was 1.80 (95% CI, 1.17-2.78) when comparing NOR with DET. Conclusions and Relevance: In this cohort study, the frequency of delayed emergency surgery in France was 32.5%. Reduced delays were found in organizational pathways that included dedicated theaters and teams. These preliminary results may pave the way for comprehensive large-scale studies, from which results may potentially inform new guidelines for quicker and safer access to emergency surgery.

Stigma and healthcare access among men who have sex with men and transgender women who have sex with men in Senegal.

Objectives: Cisgender gay, bisexual, and other men who have sex with men and transgender women experience HIV incidence disparities in Senegal. These analyses determined how depression and different stigma mechanisms related to sexual behavior are associated with healthcare access, sexually transmitted infection testing, and HIV testing among cisgender gay, bisexual, and other men who have sex with men and transgender women across three cities in western Senegal. Methods: Logistic regression assessed the relationship of three stigma scales (stigma from family and friends, anticipated healthcare stigma, and general social stigma) and depression with these outcomes. Results: Depression and stigma were not associated with healthcare access, sexually transmitted infection testing, or HIV testing. However, individuals who had disclosed their sexual identity to a medical provider were more likely to test for HIV. Conclusions: Sexual behavior stigma experienced by cisgender gay, bisexual, and other men who have sex with men and trans women in Senegal may not limit access to routine healthcare, but may limit disclosure of sexual orientation and practices, limiting access to appropriate HIV prevention services.

The hypertensive effect of sorafenib is abolished by sildenafil.

BACKGROUND: Contrasting to the well documented tyrosine kinase inhibitor (TKI)-induced hypertension, little is known on their intrinsic vasomotor effects. We investigated the vasomotor effects of sorafenib, a widely used multikinase inhibitor in the treatment of hepatocellular and renal cell carcinoma and tested the hypothesis that sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, could represent a pharmacological strategy for the treatment of TKI-induced hypertension. METHODS: Concentration-response curves of sorafenib were constructed in endothelium-intact or denuded precontracted rat aorta, in the presence or absence of several inhibitors. Acute intravenous effects of sorafenib on arterial blood pressure were also investigated in anaesthetized rats. Finally, rats were chronically treated with sorafenib during 4 weeks in the presence and absence of sildenafil. RESULTS: In endothelium intact aortic ring, sorafenib induced a potent concentration-dependent relaxation of precontracted rat aorta. Removal of the endothelium shifted the concentration-response curve of sorafenib to the right and significantly reduced its maximal effects, demonstrating that sorafenib-induced vasorelaxation is endothelium-dependent and endothelium-independent. Inhibition of the different pathways implicated in the endothelium-dependent and independent vasorelaxation revealed that the endothelium-dependent effects of sorafenib result mainly from the activation of prostaglandin and the nitric oxide (NO) pathways. The endothelium-independent vasodilatory effects of sorafenib may result mainly from the activation of Na/K-ATPase and soluble guanylate cyclase. These vasodilatory effects observed in vitro were confirmed by the decrease in arterial blood pressure observed during acute administrations of sorafenib in anesthetized rats. Finally, and most importantly, we report here for the first time that chronic administration of sorafenib in rats induced an increase in SBP that was abolished by sildenafil. CONCLUSION: The multikinase inhibitor sorafenib induced in vitro vasorelaxation of large conductance artery, primary by activating soluble guanylate cyclase. Its chronic administration led to arterial blood hypertension that was counteracted by a PDE-5 inhibitor, sildenafil. Our results suggest that targeting the cGMP pathway including NO signalling might be an interesting pharmacological strategy for the treatment of TKI-induced hypertension.

Characterizing social cohesion and gender identity as risk determinants of HIV among cisgender men who have sex with men and transgender women in Côte d'Ivoire.

PURPOSE: HIV prevalence has been previously estimated among cisgender men who have sex with men (MSM) in Côte d'Ivoire; however, limited data exist relating to the role of social cohesion and gender identity within this population. This study aims to examine these factors as risk determinants of HIV among MSM in Côte d'Ivoire. METHODS: We conducted a cross-sectional study using respondent-driven sampling for recruitment with a structured sociobehavioral instrument and testing for HIV. After respondent-driven sampling adjustment, chi-squared tests and bivariate logistic regression and multivariate logistic regression analyses were performed to characterize social and identity-based risk determinants of biologically confirmed prevalent HIV infection. RESULTS: HIV prevalence was 11.2% (n = 146/1301). Transgender woman identity was associated with higher odds of HIV compared with cisgender MSM (aOR = 3.4, 95% CI [2.0-5.8], P < .001). Having a combined social cohesion score of medium (aOR = 0.4, 95% CI [0.2-0.8], P < .01) or high (aOR = 0.2, 95% CI [0.1-0.3], P < .001) was associated with lower odds of HIV compared with a low score. CONCLUSION: These data suggest that social cohesion is a determinant of prevalent HIV infection in Côte d'Ivoire among gay men, other cisgender MSM, and transgender women. The differences in HIV burden and social cohesion between transgender women and cisgender MSM highlight the need to better target the diversity of people traditionally included in the MSM umbrella to ensure comprehensive HIV prevention and treatment interventions.

The role of sex work laws and stigmas in increasing HIV risks among sex workers.

Globally HIV incidence is slowing, however HIV epidemics among sex workers are stable or increasing in many settings. While laws governing sex work are considered structural determinants of HIV, individual-level data assessing this relationship are limited. In this study, individual-level data are used to assess the relationships of sex work laws and stigmas in increasing HIV risk among female sex workers, and examine the mechanisms by which stigma affects HIV across diverse legal contexts in countries across sub-Saharan Africa. Interviewer-administered socio-behavioral questionnaires and biological testing were conducted with 7259 female sex workers between 2011-2018 across 10 sub-Saharan African countries. These data suggest that increasingly punitive and non-protective laws are associated with prevalent HIV infection and that stigmas and sex work laws may synergistically increase HIV risks. Taken together, these data highlight the fundamental role of evidence-based and human-rights affirming policies towards sex work as part of an effective HIV response.

Intersectional stigmas and HIV-related outcomes among a cohort of key populations enrolled in stigma mitigation interventions in Senegal.

OBJECTIVES: The current study aims to assess longitudinal differences in stigma and HIV outcomes among key populations at risk for and living with HIV. DESIGN: Key populations enrolled into two parallel prospective cohorts; one for female sex workers and one for sexual and gender minorities (SGMs). Participants were recruited from three urban areas in Senegal; were followed for 24 months; and had the option to participate in an integrated stigma mitigation intervention. METHODS: Participants included individuals both at risk for and living with HIV. Sociobehavioral questionnaires and biological HIV testing were administered every 3-4 months. Longitudinal analyses used nonparametric Chi-squared test for trends and multivariable logistic regression with generalized estimating equations. RESULTS: 183 SGM and 192 sex workers were enrolled. Among SGM participants, 39.9% were living with HIV at baseline and incidence over 24 months was 3.21/100 person-years. Among sex workers, 36.6% were living with HIV at baseline and incidence was 1.32/100 person-years. Among SGM, perceived healthcare stigma (P < 0.001), anticipated healthcare stigma (P < 0.001), and perceived friend stigma (P = 0.047) reduced, but differed by HIV status for perceived [adjusted odds ratio (aOR): 3.51; 95% confidence interval (CI): 1.75, 7.06] and anticipated healthcare stigmas (aOR: 2.85; 95% CI: 1.06-7.67). Among sex workers perceived healthcare stigma (P = 0.043) and perceived friend stigma (P = 0.006) reduced. Viral suppression increased among SGM (P = 0.028) and was associated with perceived (aOR: 2.87; 95% CI: 1.39-5.55) and enacted healthcare stigma (aOR: 0.42; 95% CI: 0.18-0.99). CONCLUSION: Overall, there were decreases in stigmas observed but clear differences in stigma patterns by HIV status. These data highlight the need to consider specific strategies to address multiple intersecting stigmas as a means of improving HIV-related prevention and treatment outcomes among key populations with diverse identities.

Sexual behavior stigma and depression among transgender women and cisgender men who have sex with men in Côte d'Ivoire.

PURPOSE: Transgender women (TGW) and cisgender men who have sex with men (cisMSM) across sub-Saharan Africa experience health inequalities relative to other adults. Recent research has also revealed health inequalities between these often-conflated groups. Among TGW and cisMSM in Côte d'Ivoire, we sought to determine whether transgender female identity was associated with probable depression, and whether sexual behavior stigma mediated this association. METHODS: In 2015-2016, a cross-sectional respondent-driven sampling survey of adult TGW and cisMSM was conducted across five cities. We conducted a three-way decomposition of mediation and interaction of gender identity and sexual behavior stigma. Depression was measured by the nine-item Patient Health Questionnaire (PHQ-9). RESULTS: Of 1301 participants, 339 (26.1%) were TGW. The prevalence of probable depression was 22.7% among TGW and 12.2% among cisMSM (P < .001). After confounder adjustment, the relative risk of depression attributable to transgender female gender identity was 1.68 (95% CI = 1.36, 2.00) with 69.9% (95% CI = 42.6, 97.1) of this effect mediated by sexual behavior stigma. The effect of stigma on depression did not differ significantly by gender. CONCLUSIONS: These data suggest that stigma mitigation interventions specifically addressing the stigma affecting transgender women may also address mental health inequalities between transgender women and cisMSM in Côte d'Ivoire.

Characterizing the Influence of Structural Determinants of HIV Risk on Consistent Condom Use Among Female Sex Workers in Senegal.

BACKGROUND: Female sex workers (FSWs) are disproportionately affected by HIV even in the most generalized HIV epidemics. Although structural HIV risks have been understood to affect condom negotiation among FSWs globally, there remain limited data on the relationship between structural determinants of HIV risk, including violence and socioeconomic status, and condom use among FSWs across sub-Saharan Africa. Here, we describe the prevalence of structural determinants and their associations with condom use among FSWs in Senegal. METHODS: In 2015, 758 FSWs >18 years of age were recruited using respondent driven sampling in Senegal. Data on individual, community, network, and structural-level risks were collected through an interviewer-administered questionnaire. Poisson regression with robust variance estimation was used to model the associations of consistent condom use (CCU) and selected structural determinants. RESULTS: The respondent driven sampling-adjusted prevalence of CCU in the last 10 sexual acts was 76.8% [95% confidence interval (CI): 70.8 to 82.8]. Structural determinants that were significantly associated with lower CCU were as follows: physical violence [adjusted prevalence ratio (aPR): 0.71; 95% CI: 0.52 to 0.98]; working primarily in a hotel or guest house (aPR: 0.85; 95% CI: 0.73 to 0.99); and difficultly accessing condoms (aPR: 0.72; 95% CI: 0.52 to 0.96). High income from sex work (aPR: 1.23; 95% CI: 1.04 to 1.46) was significantly associated with higher CCU. CONCLUSIONS: Taken together, these data highlight the role of structural risk determinants on condom use among FSWs in Senegal. Moreover, these results highlight the need for structural interventions, including safe working spaces and violence mitigation programs, to support condom negotiation and access. Combined with condom distribution programs, structural interventions could ultimately increase condom use among FSWs in Senegal.

Estimating the contribution of key populations towards the spread of HIV in Dakar, Senegal.

INTRODUCTION: Key populations including female sex workers (FSW) and men who have sex with men (MSM) bear a disproportionate burden of HIV. However, the role of focusing prevention efforts on these groups for reducing a country's HIV epidemic is debated. We estimate the extent to which HIV transmission among FSW and MSM contributes to overall HIV transmission in Dakar, Senegal, using a dynamic assessment of the population attributable fraction (PAF). METHODS: A dynamic transmission model of HIV among FSW, their clients, MSM and the lower-risk adult population was parameterized and calibrated within a Bayesian framework using setting-specific demographic, behavioural, HIV epidemiological and antiretroviral treatment (ART) coverage data for 1985 to 2015. We used the model to estimate the 10-year PAF of commercial sex between FSW and their clients, and sex between men, to overall HIV transmission (defined as the percentage of new infections prevented when these modes of transmission are removed). In addition, we estimated the prevention benefits associated with historical increases in condom use and ART uptake, and impact of further increases in prevention and treatment. RESULTS: The model projections suggest that unprotected sex between men contributed to 42% (2.5 to 97.5th percentile range 24 to 59%) of transmissions between 1995 and 2005, increasing to 64% (37 to 79%) from 2015 to 2025. The 10-year PAF of commercial sex is smaller, diminishing from 21% (7 to 39%) in 1995 to 14% (5 to 35%) in 2015. Without ART, 49% (32 to 71%) more HIV infections would have occurred since 2000, when ART was initiated, whereas without condom use since 1985, 67% (27 to 179%) more HIV infections would have occurred, and the overall HIV prevalence would have been 60% (29 to 211%) greater than what it is now. Further large decreases in HIV incidence (68%) can be achieved by scaling up ART in MSM to 74% coverage and reducing their susceptibility to HIV by two-thirds through any prevention modality. CONCLUSIONS: Unprotected sex between men may be an important contributor to HIV transmission in Dakar, due to suboptimal coverage of evidence-informed interventions. Although existing interventions have effectively reduced HIV transmission among adults, it is crucial that further strategies address the unmet need among MSM.