Pathways to Poor Adherence to Antiretroviral Therapy Among People Living with HIV: The Role of Food Insecurity and Alcohol Misuse.

Daily adherence to antiretroviral therapy (ART) increases the length and quality of life of people living with HIV (PLHIV). We explored whether socioeconomic status directly impacts ART adherence and whether part of the effect is mediated by pathways through alcohol misuse or food insecurity. A cross-sectional study was conducted in Rio de Janeiro/Brazil (November/2019 to March/2020) with PLHIV aged ≥ 18 years. Validated instruments were used to measure alcohol use, food insecurity, and ART adherence. Using structural equation modeling we assessed the direct and indirect effects of variables on ART adherence. Participants reported significant challenges: hunger: 12%, alcohol use: 64%, and missing ART doses: 24%. Results showed that lower socioeconomic status increased poor adherence and that this effect was mediated through higher food insecurity. Alcohol misuse also increased poor adherence through a strong direct effect. Providing socio-economic support coupled with interventions to mitigate alcohol's harmful impact can aid HIV care.

RESUMEN: La adherencia diaria a la terapia antirretroviral (TAR) aumenta la duración y calidad de vida de las personas que viven con el VIH (PVVIH). Exploramos si el estatus socioeconómico afecta directamente la adherencia al TAR y si parte del efecto está mediado por vías a través del abuso del alcohol o la inseguridad alimentaria. Se realizó un estudio en Río de Janeiro/Brasil (noviembre/2019 a marzo/2020) con PVVIH con edad ≥ 18 años. Utilizando modelos de ecuaciones estructurales evaluamos los efectos directos e indirectos. Los participantes informaron desafíos significativos: hambre: 12%, consumo de alcohol: 64%, mala adherencia: 24%. Los resultados mostraron que un nivel socioeconómico más bajo aumentaba la mala adherencia por un efecto mediado por mayor inseguridad alimentaria. Abuso de alcohol también aumentó la mala adherencia por un fuerte efecto directo. Brindar apoyo socioeconómico con intervenciones para mitigar el impacto nocivo del alcohol puede ayudar la atención clínica.

HIV Treatment Optimism Moderates the Relationship between Sexual Risk Behavior and HIV Risk Perception among Urban HIV-negative Gay, Bisexual, and Other Men who have Sex With Men.

Using baseline data of the Engage Cohort Study, a Canadian study of sexually active gay, bisexual and other men who have sex with men (GBM), we evaluated the association between sexual behavior and risk perception among HIV-negative participants and whether HIV treatment optimism moderated this relationship. Participants were recruited by respondent-driven-sampling (RDS). We defined high-risk sexual behavior in the past six months as any condomless anal sex with a casual partner (i.e. not the participant's main partner) with either unknown HIV-status where neither used pre-exposure prophylaxis or with a partner living with HIV having detectable/unknown viral load. We assessed HIV treatment optimism-skepticism using a 12-item scale. RDS-II-weighted adjusted logistic regression models examined associations with risk perception measured by the question "How would you assess your current risk of getting HIV?" (response options were on a 6-point Likert-scale ranging from "very unlikely" to "very likely", dichotomized into "No Perceived Risk" (very unlikely/unlikely) and "Perceived Risk" (somewhat likely/likely/very likely/I think I already have HIV). Of 1961 participants, engagement in high-risk sexual behavior was reported by 155 (17.0%), 62 (12.4%), 128 (17.2%) of participants in Montréal, Toronto, and Vancouver, respectively. High-risk sexual behavior increased the odds of perceived HIV risk (pooled adjusted odds ratio = 2.9, 95%CI = 2.2-3.8). HIV treatment optimism-skepticism scores moderated the relationship: for GBM engaging in high-risk sexual behavior, higher HIV treatment optimism-skepticism scores increased perceived HIV risk. Promoting awareness around advances related to HIV prevention and treatment is important for appropriate risk assessment and for increased engagement in prevention interventions.

RESUMEN: Evaluamos la asociación entre el comportamiento sexual y la percepción de riesgo entre los participantes VIH negativos y si el optimismo sobre el tratamiento del VIH moderó esta asociación. Definimos comportamiento sexual de alto riesgo en los últimos seis meses como cualquier sexo anal sin condón con una pareja casual con un estado de VIH desconocido donde ninguno utilizó profilaxis previa a la exposición o con una pareja que vive con el VIH y que tiene una carga viral detectable/desconocida. Se evaluó el optimismo sobre el tratamiento del VIH mediante una escala de 12 ítems. Los modelos de regresión logística ajustados examinaron las asociaciones con la percepción del riesgo ("Riesgo no percibido" vs. "Riesgo percibido"). De 1961 participantes, 155 (17,0%), 62 (12,4%), 128 (17,2%) de los participantes en Montreal, Toronto y Vancouver, informaron comportamiento sexual de alto riesgo. El comportamiento sexual de alto riesgo se mostró asociado con riesgo percibido. El optimismo sobre el tratamiento modero la asociación. Promover la conciencia sobre los avances relacionados con la prevención y el tratamiento del VIH es importante para una evaluación adecuada de los riesgos y una mayor participación en las intervenciones de prevención.

Perceived risk for HIV acquisition and sexual HIV exposure among sexual and gender minorities: a systematic review.

We conducted a systematic review to explore the relationship between perceived risk for HIV acquisition and sexual HIV exposure among sexual and gender minorities. We included 39 studies divided into (i) correlations or associations, (ii) models using sexual HIV exposure as the outcome, and (iii) models using perceived risk for HIV acquisition as the outcome. The sample size range was from 55 to 16,667 participants, primarily cisgender men who have sex with men (73.3%) and White (51.3%). Sexual HIV exposure and perceived risk for HIV acquisition assessments and recall time frames across studies differed markedly. Most of studies (84.6%) found significant correlations, comparisons, or associations between different levels of perceived risk for HIV acquisition and high sexual HIV exposure. In addition, 51.3% of studies reported other variables associated with high sexual HIV exposure (i.e., misuse of substances or alcohol) or with high perceived risk for HIV acquisition (i.e., younger age). In conclusion, the association between perceived risk for HIV acquisition and sexual HIV exposure has shown to be consistent. However, the assessment for perceived risk for HIV acquisition should include more components of perception (i.e., an affective component), or for sexual HIV exposure should consider the different estimated sexual per-acts probability of acquiring HIV.

The Impact of COVID-19 on HIV Care in Rio de Janeiro, Brazil 2019-2021: Disparities by Age and Gender.

We evaluated COVID-19's impact on HIV care indicators among INI/FIOCRUZ's HIV Clinical Cohort in Rio de Janeiro, Brazil: (1) Adequate care visits: two visits ≥ 90 days apart; (2) Adequate viral load monitoring: ≥ 2 viral load results ≥ 90 days apart; (3) Consistent viral suppression: all viral loads < 40 copies/mL; and (4) ART medication possession ratio (MPR) ≥ 95%. Chi-square tests compared the fraction of participants meeting each indicator per period: pre-pandemic (3/1/2019-2/29/2020) and post-pandemic (3/1/2020-2/28/2021). Logistic regression models were used to assess disparities in adequate care visits. Among 906 participants, care visits and viral load monitoring decreased pre-pandemic to post-pandemic: 77.0-55.1% and 36.6-11.6% (both p < 0.001), respectively. The optimal MPR rate improved from 25.5 to 40.0% (p < 0.001). Post-pandemic period (aOR 0.33, CI 0.28-0.40), transgender women (aOR 0.34, CI 0.22-0.53), and those aged 18-24 years (aOR 0.67, CI 0.45-0.97) had lower odds of adequate care visits. COVID-19 disrupted care access disproportionately for transgender women and younger participants.

Real-world effectiveness of WHO recommended first-line antiretroviral therapies: a cohort study from a middle-income country.

We estimate the effectiveness of antiretroviral therapy (ART) among individuals receiving HIV care in Rio de Janeiro, Brazil. Adults (18y+) initiating ART between Jan/2008 and Dec/2018 (follow-up through Dec/2020) were included. First-line ART (two nucleoside reverse transcriptase inhibitors plus one antiretroviral from another class) was categorized into four categories: non-nucleoside reverse transcriptase inhibitor/NNRTI-based, protease inhibitor/PI-based, integrase strand transfer inhibitor/INSTI-based, and single-tablet regimen (STR, Tenofovir 300mg + Lamivudine 300mg + Efavirenz 600mg). Effectiveness (viral load ≤50 copies/µL) was evaluated at 6(3-9) and 12(9-15) months from ART initiation. Bayesian logistic regression models were used to quantify the association between exposure and outcomes while accounting for missing data. Overall, 1863(57%), 652(19.9%), 412(12.6%), and 342(10.5%) individuals used, respectively, NNRTI-based, PI-based, INSTI-based regimens, and STR. Compared to NNRTIs, the odds of viral suppression with INSTI-based regimens was 76% higher (adjusted OR:1.76, 95%CI:1.23-2.51) at six months but no higher at 12 months. Older age, higher education, CD4 count ≥500 cells/mm3 and viral load <100,000 copies/µL at ART initiation increased the odds of viral suppression. Viral suppression at six months was the strongest predictor of viral suppression at 12 months. These results highlight population groups that could benefit from close monitoring during the first year of ART.

Impact of pre-exposure prophylaxis uptake among gay, bisexual, and other men who have sex with men in urban centers in Brazil: a modeling study.

BACKGROUND: Men who have sex with men (MSM) in Brazil remain disproportionately affected by HIV. We estimated the potential incidence reduction by five years with increased uptake of publicly-funded, daily, oral tenofovir/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) among MSM using the Cost Effectiveness of Preventing AIDS Complications microsimulation model. We used national data, local studies, and literature to inform model parameters for three cities: Rio de Janeiro, Salvador, and Manaus. RESULTS: In Rio de Janero, a PrEP intervention achieving 10% uptake within 60 months would decrease incidence by 2.3% whereas achieving 60% uptake within 24 months would decrease incidence by 29.7%; results were similar for Salvador and Manaus. In sensitivity analyses, decreasing mean age at PrEP initiation from 33 to 21 years increased incidence reduction by 34%; a discontinuation rate of 25% per year decreased it by 12%. CONCLUSION: Targeting PrEP to young MSM and minimizing discontinuation could substantially increase PrEP's impact.

Differential Type-I Interferon Response in Buffy Coat Transcriptome of Individuals Infected with SARS-CoV-2 Gamma and Delta Variants.

The innate immune system is the first line of defense against pathogens such as the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The type I-interferon (IFN) response activation during the initial steps of infection is essential to prevent viral replication and tissue damage. SARS-CoV and SARS-CoV-2 can inhibit this activation, and individuals with a dysregulated IFN-I response are more likely to develop severe disease. Several mutations in different variants of SARS-CoV-2 have shown the potential to interfere with the immune system. Here, we evaluated the buffy coat transcriptome of individuals infected with Gamma or Delta variants of SARS-CoV-2. The Delta transcriptome presents more genes enriched in the innate immune response and Gamma in the adaptive immune response. Interactome and enriched promoter analysis showed that Delta could activate the INF-I response more effectively than Gamma. Two mutations in the N protein and one in the nsp6 protein found exclusively in Gamma have already been described as inhibitors of the interferon response pathway. This indicates that the Gamma variant evolved to evade the IFN-I response. Accordingly, in this work, we showed one of the mechanisms that variants of SARS-CoV-2 can use to avoid or interfere with the host Immune system.

Multilevel Analysis of Individual and Neighborhood Characteristics Associated with Viral Suppression Among Adults with HIV in Rio de Janeiro, Brazil.

Understanding the impact of neighborhood context on viral suppression outcomes may help explain health disparities and identify future interventions. We assessed the relationship between individual characteristics, neighborhood socioeconomic context, and viral suppression using multilevel logistic regression models. Adults with HIV initiating antiretroviral therapy (ART) between 2000 and 2017, who resided in Rio de Janeiro and had an HIV-1 RNA level (viral load) measured 90-270 days after ART initiation were included. Overall, 83.9% achieved viral suppression. Participants who were older, had a higher level of education, and identified as heterosexual cisgender men and cisgender men-who-have-sex-with-men had increased odds of viral suppression. Later calendar year of ART initiation carried the strongest association with viral suppression, reflecting the increased effectiveness and tolerability of ART over time. Neighborhood socioeconomic indicators did not predict viral suppression in unadjusted or adjusted analyses, which may result from the integrated care provided in our health care facility together with Brazil's universal treatment.

RESUMEN: Comprender el impacto del contexto representado por el lugar de residencia o vecindario sobre los resultados de supresión viral puede ayudar a explicar las disparidades en salud e identificar futuras intervenciones. Evaluamos la relación entre las características individuales, el contexto socioeconómico del vecindario y la supresión viral utilizando modelos de regresión logística multinivel. Incluimos adultos con VIH que comenzaron terapia antiretroviral (ART) entre los años 2000 y 2017, que residían en Río de Janeiro y tenían un valor de nivel de ARN del VIH-1 (carga viral) medido 90-270 días después del inicio de la ART. En general, el 83.9% logró supresión viral. Los participantes con mayor de edad, mayor nivel de educación, identificados como hombres cisgénero heterosexuales y hombres cisgénero que tienen sexo con hombres tenían mayores probabilidades de supresión viral. Los años calendario más recientes de inicio de ART tuvieron la asociación más fuerte con supresión viral, lo que refleja el incremento de la efectividad y la tolerancia a los antirretrovirales con el paso del tiempo. Los indicadores socioeconómicos del vecindario no predijeron supresión viral en los análisis no ajustados o ajustados, que puede resultar de la atención integrada en nuestro centro de salud junto con el tratamiento universal de Brasil.

Early mortality in a cohort of people living with HIV in Rio de Janeiro, Brazil, 2004-2015: a persisting problem.

BACKGROUND: Global mortality from AIDS-related diseases has been declining since 2005, resulting primarily from the widespread use and early initiation of combination antiretroviral therapy. Despite the significant improvements, high rates of early mortality, usually defined as that occurring within the 1st year of entry to care, have been observed, especially in resource-limited settings. This analysis draws upon data from an observational cohort of people with HIV (PWH) followed at a reference center for HIV/AIDS care and research in the city of Rio de Janeiro, Brazil, to identify the pattern and factors associated with early mortality. METHODS: The study population includes PWH aged 18 or older followed at the National Institute of Infectious Diseases Evandro Chagas who were enrolled between 2004 and 2015. The primary outcome was early mortality, defined as deaths occurring within 1 year of inclusion in the cohort, considering two follow-up periods: 0 to 90 days (very early mortality) and 91 to 365 days (early mortality). Cox proportional hazards models were used to identify the variables associated with the hazard of very early and early mortality. RESULTS: Overall, 3879 participants contributed with 3616.4 person-years of follow-up. Of 220 deaths, 132 happened in the first 90 days and 88 between 91 and 365 days. Very early mortality rate ratios (MRR) show no statistically significant temporal differences between the periods 2004-2006 to 2013-2015. In contrast, for early mortality, a statistically significant decreasing trend was observed: mortality rates in the periods 2004-2006 (MR = 5.5; 95% CI 3.9-7.8) and 2007-2009 (MR = 3.9; 95% CI 2.7-5.7) were approximately four and three-fold higher when compared to 2013-2015 (MR = 1.4; 95% CI 0.7-2.7). Low CD4 count and prior AIDS-defining illness were strongly associated with higher hazard ratios of death, especially when considering very early mortality. CONCLUSIONS: The present study shows an excess of mortality in the 1st year of follow-up with no changes in the mortality rates within 90 days among PWH from Rio de Janeiro. We note the significant impact of initiating treatment with immunosuppression, as evidenced by the increased risk of death among those with low CD4 cell count and with AIDS-defining illnesses.

Effects of National Adoption of Treat-All Guidelines on Pre-Antiretroviral Therapy (ART) CD4 Testing and Viral Load Monitoring After ART initiation: A Regression Discontinuity Analysis.

BACKGROUND: The World Health Organization's Treat-All guidance recommends CD4 testing before initiating antiretroviral therapy (ART), and routine viral load (VL) monitoring (over CD4 monitoring) for patients on ART. METHODS: We used regression discontinuity analyses to estimate changes in CD4 testing and VL monitoring among 547 837 ART-naive patients enrolling in human immunodeficiency virus (HIV) care during 2006-2018 at 225 clinics in 26 countries where Treat-All policies were adopted. We examined CD4 testing within 12 months before and VL monitoring 6 months after ART initiation among adults (≥20 years), adolescents (10-19 years), and children (0-9 years) in low/lower-middle-income countries (L/LMICs) and high/upper-middle-income countries (H/UMICs). RESULTS: Treat-All adoption led to an immediate decrease in pre-ART CD4 testing among adults in L/LMICs, from 57.0% to 48.1% (-8.9 percentage points [pp]; 95% CI: -11.0, -6.8), and a small increase in H/UMICs, from 90.1% to 91.7% (+1.6pp; 95% CI: 0.2, 3.0), with no changes among adolescents or children; decreases in pre-ART CD4 testing accelerated after Treat-All adoption in L/LMICs. In L/LMICs, VL monitoring after ART initiation was low among all patients in L/LMICs before Treat-All; while there was no immediate change at Treat-All adoption, VL monitoring trends significantly increased afterwards. VL monitoring increased among adults immediately after Treat-All adoption, from 58.2% to 61.1% (+2.9pp; 95% CI: 0.5, 5.4), with no significant changes among adolescents/children. CONCLUSIONS: While on-ART VL monitoring has improved in L/LMICs, Treat-All adoption has accelerated and disparately worsened suboptimal pre-ART CD4 monitoring, which may compromise care outcomes for individuals with advanced HIV.

High-Risk Sexual Behavior, Binge Drinking and Use of Stimulants are Key Experiences on the Pathway to High Perceived HIV Risk Among Men Who Have Sex with Men in Brazil.

In Brazil, pre-exposure prophylaxis (PrEP) is currently available for gay, bisexual, and other men who have sex with men. As PrEP use depends on an individual's perceived risk, we explored pathways by which potentially modifiable behaviors lead to high perceived HIV risk. Using online surveys (N = 16,667), we conducted a path analysis on the basis of ordered sequences of multivariate logistic regressions. High perceived HIV risk was low (26.3%) compared to condomless receptive anal sex (41.4%). While younger age increased the odds of binge drinking and of condomless receptive anal sex, it was associated with decreased odds of high perceived HIV risk. In contrast, use of stimulants increased the odds of condomless receptive anal sex and of high perceived HIV risk. Our results suggest that binge drinking and use of stimulants are key points in different pathways to high-risk sexual behavior and may lead to different perceptions of HIV risk.

RESUMEN: En Brasil, la profilaxis previa a la exposición (PrEP) está disponible actualmente para hombres homosexuales, bisexuales y otros hombres que tienen sexo con hombres. Como el uso de PrEP depende del riesgo percibido de una persona, exploramos vías por las cuales los comportamientos potencialmente modificables conducen a un alto riesgo percibido de VIH. Utilizando datos de encuestas en línea (N = 16.667), realizamos un análisis de ruta sobre la base de secuencias ordenadas de regresiones logísticas multivariadas. El alto riesgo percibido de VIH fue bajo (26,3%) en comparación con el sexo anal receptivo sin condón (41,4%). La edad más joven aumentó las probabilidades de consumo de alcohol en exceso y del sexo anal receptivo sin condón, todavía se asoció con una menor probabilidad de alta percepción de riesgo sobre VIH. Sin embargo, el uso de estimulantes aumentó las probabilidades de tener sexo anal receptivo sin condón y de un alto riesgo percibido de VIH. Nuestros resultados sugieren que el consumo excesivo de alcohol y el uso de estimulantes son puntos clave en diferentes vías de conductas sexuales de alto riesgo y pueden llevar a diferentes percepciones del riesgo de VIH.

Cross-cultural adaptation of the Perceived Risk of HIV Scale in Brazilian Portuguese.

BACKGROUND: Valid and reliable instruments are needed to measure the multiple dimensions of perceived risk. The Perceived Risk of HIV Scale is an 8-item measure that assesses how people think and feel about their risk of infection. We set out to perform a cross-cultural adaptation of the scale to Brazilian Portuguese among key populations (gay, bisexual and other men who have sex with men and transgender/non-binary) and other populations (cisgender heterosexual men and cisgender women). METHODS: Methodological study with cross-sectional design conducted online during October/2019 (key populations [sample 1] and other populations) and February-March/2020 (key populations not on pre-exposure prophylaxis [sample 2]). Cross-cultural adaptation of the Perceived Risk of HIV Scale followed Beaton et al. 2000 guidelines and included confirmatory factor analysis, differential item functioning (DIF) using the Multiple-Indicator Multiple-Cause model, and concurrent validity to verify if younger individuals, those ever testing for HIV, and engaging in high-risk behaviors had higher scores on the scale. RESULTS: 4342 participants from key populations (sample 1 = 235; sample 2 = 4107) and 155 participants from other populations completed the measure. We confirmed the single-factor structure of the original measure (fit indices for sample 1 plus other populations: CFI = 0.98, TLI = 0.98, RMSEA = 0.07; sample 2 plus other populations: CFI = 0.97, TLI = 0.95, RMSEA = 0.09). For the comparisons between key populations and other populations, three items (item 2: "I worry about getting infected with HIV", item 4: "I am sure I will not get infected with HIV", and item 8: "Getting HIV is something I have") exhibited statistically significant DIF. Items 2 and 8 were endorsed at higher levels by key populations and item 4 by other populations. However, the effect of DIF on overall scores was negligible (0.10 and 0.02 standard deviations for the models with other populations plus sample 1 and 2, respectively). Those ever testing for HIV scored higher than those who never tested (p < .001); among key populations, those engaging in high-risk behaviors scored higher than those reporting low-risk. CONCLUSION: The Perceived Risk of HIV Scale can be used among key populations and other populations from Brazil.

Late initiation of antiretroviral therapy: inequalities by educational level despite universal access to care and treatment.

BACKGROUND: Late antiretroviral treatment initiation for HIV disease worsens health outcomes and contributes to ongoing transmission. We investigated whether socioeconomic inequalities exist in access to treatment in a setting with universal access to care and treatment. METHODS: This study investigated the association of educational level, used as a proxy for socioeconomic status, with late treatment initiation and treatment initiation with advanced disease. Study participants included adults (≥25 years) who started treatment from 2005 to 2018 at Instituto Nacional de Infectologia Evandro Chagas of Fundação Oswaldo Cruz (INI/FIOCRUZ), Rio de Janeiro, Brazil. Educational level was categorized following UNESCO's International Standard Classification of Education: incomplete basic education, basic education, secondary level, and tertiary level. We defined late treatment initiation as those initiating treatment with a CD4 < 350 cells/mL or an AIDS-defining event, and treatment initiation with advanced disease as those initiating treatment with a CD4 < 200 cells/mL or an AIDS-defining event. A directed acyclic graph (DAG) was constructed to represent the theoretical-operational model and to understand the involvement of covariates. Logistic regression models were used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). Multiple imputation using a chained equations approach was used to treat missing values and non-linear terms for continuous variables were tested. RESULTS: In total, 3226 individuals composed the study population: 876 (27.4%) had incomplete basic education, 540 (16.9%) basic, 1251 (39.2%) secondary level, and 525 (16.4%) tertiary level. Late treatment initiation was observed for 2076 (64.4%) while treatment initiation with advanced disease was observed for 1423 (44.1%). Compared to tertiary level of education, incomplete basic, basic and secondary level increased the odds of late treatment initiation by 89% (aOR:1.89 95%CI:1.47-2.43), 61% (aOR:1.61 95%CI:1.23-2.10), and 35% (aOR:1.35 95%CI:1.09-1.67). Likewise, the odds of treatment initiation with advanced disease was 2.5-fold (aOR:2.53 95%CI:1.97-3.26), 2-fold (aOR:2.07 95%CI:1.59-2.71), 1.5-fold (aOR:1.51 95%CI:1.21-1.88) higher for those with incomplete basic, basic and secondary level education compared to tertiary level. CONCLUSION: Despite universal access to HIV care and antiretroviral treatment, late treatment initiation and social inequalities persist. Lower educational level significantly increased the odds of both outcomes, reinforcing the existence of barriers to "universal" antiretroviral treatment.

Translation and validation in Brazilian Portuguese of the reactions to homosexuality scale.

Internalized homonegativity results from the acceptance of negative attitudes about one's same-sex orientation, which has negative consequences for the health of gay, bisexual and other men who have sex with men (GBM). We translated the 7-item Reactions to Homosexuality Scale (RHS) to Brazilian Portuguese and assessed its factor structure, validity and reliability. The first step included the translation, back-translation, evaluation, peer review, and pre-testing of the scale. Then, we piloted the scale in two convenience samples of adult Brazilians recruited online during October 2019 and February to March 2020 through advertisements on Grindr and Hornet, respectively. The largest sample was randomly split into two groups for exploratory factor analysis (EFA) then confirmatory factor analysis (CFA). Criterion and construct validity were assessed via correlations between scale scores and study variables. A total of 5573 GBM (sample 1: 218; sample 2: 5355) completed the RHS. EFA (N = 2652) yielded two eigenvalues greater than one (Factor 1: 3.5 and Factor 2: 1.1). A one-factor solution provided the most interpretable model based on examination of scree plot and item factor loadings (χ2(14) = 1373.1, p < 0.001; CFI = 0.89; TLI = 0.84; RMSEA = 0.19; SRMS = 0.09). Though one-factor CFA showed moderate fit, freeing errors terms to covary, based on item content and interpretation, significantly improved model fit (χ2(12) = 309.1, p < .001; CFI = 0.97; TLI = 0.96; RMSEA = 0.09; SRMR = 0.02). As hypothesized, men who did not self-identify as gay (mean score 17.9 compared to those self-identifying as gay: 11.8) and men who reported no sex with men in the past 6 months (mean score 12.6 compared to those who reported sex with men: 10.6) scored higher reflecting higher internalized homonegativity. The RHS was effectively translated and validated in Brazilian Portuguese and can be used to evaluate the role of internalized homonegativity on GBM's health, as well as its impact on the uptake of HIV prevention technologies.

Effectiveness of direct-acting agents for chronic hepatitis C treatment in South America: A systematic review and meta-analysis.

The effectiveness of direct-acting agents (DAAs) for hepatitis C treatment in limited-resource settings remains unclear. We estimated the pooled sustained virological response rates of DAA therapy in South America. We searched online databases for studies that reported 12-week sustained virological response (SVR12) to hepatitis C virus (HCV) treatment in individuals living in South America. Pooled SVR12 in intention-to-treat (ITT) and per-protocol were estimated. Additionally, using all studies with available data, the pooled relative risk (RR) of SVR12 using a random-effects model (DerSimonian-Laird) was estimated to compare effectiveness of DAAs in patients with or without cirrhosis, HIV co-infection or previous HCV therapy. Heterogeneity was assessed using the I2 statistics. We identified 20 studies [14 manuscripts and 6 conference abstracts] comprising 7393 individuals from five countries [Brazil (n = 11), Argentina (n = 4), Chile (n = 1), Colombia (n = 1) and Peru (n = 1)] and two South-American collaborations. The pooled overall SVR12 rates [95% confidence interval (CI)] were 92.6% [90.2-94.7] and 95.5% [94.3-96.6] by ITT (11 studies; n = 4,153; I2  = 84.2%) and per-protocol analysis (15 studies; n = 4,833; I2  = 64.5%), respectively. The RR of SVR12 was similar in patients with or without HIV co-infection [4 studies; RR = 1.03 (0.99-1.07)] and those naive compared with treatment experimented-individuals [9 studies; RR = 1.01 (1.00-1.03)], but significantly higher in patients without cirrhosis compared with those with cirrhosis [11 studies; RR = 1.04 (1.02-1.05), P < .001]. DAAs are highly effective for HCV treatment in South America. The use of DAAs should be considered in limited-resource settings to decrease the burden of liver disease in HCV-infected patients. PROSPERO[CRD 42019134603].

Effectiveness of generic direct-acting agents for the treatment of hepatitis C: systematic review and meta-analysis.

OBJECTIVE: To compare the efficacy of generic direct-acting agents and brand-name medicines for treating hepatitis C virus (HCV) infection by conducting a systematic review and meta-analysis. METHODS: We searched online databases for studies that reported sustained virological responses 12 weeks after the end of HCV treatment with generic direct-acting agents. We derived pooled proportions of treated patients with a sustained virological response from intention-to-treat and per-protocol analyses. In addition, we calculated the pooled relative risk (RR) of a sustained virological response brand-name versus generic direct-acting agents using a random-effects model (DerSimonian-Laird) from the data available. Between-study heterogeneity was assessed using the I2 statistic. FINDINGS: We identified 19 studies involving a total of 57 433 individuals from eight territories or regions. The pooled overall proportions of patients with a sustained virological response were 98% (95% confidence interval, CI: 97-99; 18 studies; I2 = 94.1%) in per-protocol analyses and 96% (95% CI: 93-98; 8 studies; I2 = 68.1%) in intention-to-treat analyses. The likelihood of a sustained virological response with brand-name medicines was similar to that with generic direct-acting agents (RR: 1.00; 95% CI: 0.98-1.02; I2 = 0.0%). The likelihood of a sustained virological response was significantly higher in patients without than with cirrhosis (RR:1.03; 95% CI: 1.01-1.06; 7 studies) but was not significantly affected by either previous treatment (3 studies) or human immunodeficiency virus coinfection (3 studies). CONCLUSION: Generic direct-acting agents are highly effective for treating hepatitis C. Generic agents should be considered in resource-constrained settings for decreasing the burden of liver disease in HCV-infected patients.

Translation and validation of the Short HIV Stigma scale in Brazilian Portuguese.

BACKGROUND: HIV-related stigma, or the degree to which people living with HIV endorse negative stereotypes associated with HIV, is associated with poor continuum of care outcomes. We translated the 12-item Short HIV Stigma scale and evaluated its psychometric properties in a Brazilian context with regard to construct validity and reliability. METHODS: The first step included translation, back-translation, evaluation, peer review, and pre-testing of the Short HIV Sigma scale developed by Reinius et al. (Health Qual Life Outcomes 15(1):115, 2017). The second step involved piloting the scale in three convenience samples of adults recruited online through advertisements on different platforms: Grindr (October/2019) and Hornet (February-March/2020), geospatial network apps for sexual encounters for gay, bisexuals and other men who have sex with men, and social media apps (Facebook and WhatsApp, October/2019). The psychometric evaluation included confirmatory factor analysis, differential item functioning using the Multiple-Indicator Multiple-Cause model, and correlations between subscale scores and antiretroviral treatment use and adherence. Reliability was assessed using Cronbach's alpha, and ordinal alpha and omega from the polychoric correlation matrix. RESULTS: In total, 114, 164, and 1824 participants completed the measure items through Grindr, social media, and Hornet, respectively. We confirmed a 4-factor structure with factors for personalized stigma (3 items), disclosure concerns (3 items), concerns with public attitudes (3 items), and negative self-image (3 items). Small differential item functioning with respect to sample was found for one item ("I feel guilty because I have HIV"), which did not substantively influence estimates of latent factor scores. Grindr and Hornet's participants scored significantly higher than social media participants on all factors except personalized stigma. Higher subscale scores correlated with antiretroviral treatment use among participants from Hornet and with lower treatment adherence in participants from Grindr and Hornet. Reliability as measured by Cronbach's alpha, ordinal alpha and omega were 0.83, 0.88 and 0.93 for the entire scale. DISCUSSION: The Brazilian Portuguese version of the Short HIV Stigma scale had satisfactory psychometric properties with present results suggesting that scores from different samples may be compared without concern that measurement differences substantively influence results though further studies with greater representation of women and heterosexual men are warranted.

The Intersection of HIV, Social Vulnerability, and Reproductive Health: Analysis of Women Living with HIV in Rio de Janeiro, Brazil from 1996 to 2016.

Comprehensive care for sexual and reproductive health (SRH) and social needs for women living with HIV remains limited globally. We aimed to assess trends in baseline sociodemographic, clinical, sexual, and reproductive characteristics among a cohort of HIV-infected women in Rio de Janeiro from 1996 to 2016. Participants were stratified into four time periods based on year of enrollment; we compared cross-sectional data from each period. Of 1361 participants (median age 36), most were black or mixed race (60.1%), unemployed (52.1%), and without secondary education (54%). Adolescent pregnancy was common (51.5%), and 18.3% reported sexual debut at < 15 years old. Nearly half (45.2%) had < 5 lifetime sexual partners, yet prior syphilis and oncogenic human papillomavirus prevalence were 10.9% and 43.1%, respectively. Lifetime prevalence of induced abortion was 30.3%, and 16% used no contraceptive method. Future research should explore interactions between social vulnerability, HIV, and poor SRH outcomes and healthcare models to alleviate these disparities.

Factors associated with PrEP awareness according to age and willingness to use HIV prevention technologies: the 2017 online survey among MSM in Brazil.

Brazil has the largest population of individuals living with HIV/AIDS in Latin America with a disproportional prevalence of infection among men who have sex with men (MSM). This study evaluated PrEP awareness by age (18-24, 25-35, ≥36 years), its associated factors and the willingness to use HIV prevention technologies among MSM using a GSN app in Brazil. Inclusion criteria were ≥18 years-old, cisgender men and HIV-negative serostatus. Of 7242 individuals, 4136 (57%) completed the questionnaire. PrEP awareness was reported by 51% (though lower among MSM aged 18-24 and ≥36 years) and its associated factors were higher family income, most friends with the same sexual orientation, high number of male sexual partners and marijuana use. HIV testing (never vs. at least once) lead to an almost 3-fold increase in the odds of PrEP awareness. High HIV risk perception led to increased PrEP awareness only among MSM aged 18-24 years. A total of 2335 (56%) was willing to use daily oral PrEP. PrEP awareness remains low in Brazil and mobile tools are key strategies to reach MSM and increase awareness of prevention technologies. Community-based interventions could add to online campaigns to reach the most vulnerable, which include young, non-white and lower-income MSM.

Correction to: Seasonal dynamics of influenza in Brazil: the latitude effect.

Following publication.