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.

Pharmacogenetic interactions of efavirenz or rifampin and isoniazid with levonorgestrel emergency contraception during treatment of HIV or tuberculosis.

OBJECTIVE: In AIDS Clinical Trials Group study A5375, a pharmacokinetic trial of levonorgestrel emergency contraception, double-dose levonorgestrel (3 mg, versus standard dose 1.5 mg) offset the induction effects of efavirenz or rifampin on plasma levonorgestrel exposure over 8 h post-dose (AUC 0-8h ). We characterized the pharmacogenetics of these interactions. METHODS: Cisgender women receiving efavirenz- or dolutegravir-based HIV therapy, or on isoniazid-rifampin for tuberculosis, were followed after a single oral dose of levonorgestrel. Linear regression models, adjusted for BMI and age, characterized associations of CYP2B6 and NAT2 genotypes (which affect plasma efavirenz and isoniazid exposure, respectively) with levonorgestrel pharmacokinetic parameters. RESULTS: Of 118 evaluable participants, 17 received efavirenz/levonorgestrel 1.5 mg, 35 efavirenz/levonorgestrel 3 mg, 34 isoniazid-rifampin/levonorgestrel 3 mg, and 32 (control group) dolutegravir/levonorgestrel 1.5 mg. There were 73 Black and 33 Asian participants. Regardless of genotype, women on efavirenz and isoniazid-rifampin had higher levonorgestrel clearance. In the efavirenz/levonorgestrel 3 mg group, CYP2B6 normal/intermediate metabolizers had levonorgestrel AUC 0-8h values similar to controls, while CYP2B6 poor metabolizers had AUC 0-8h values of 40% lower than controls. In the isoniazid-rifampin group, NAT2 rapid/intermediate acetylators had levonorgestrel AUC 0-8h values similar to controls, while NAT2 slow acetylators had AUC 0-8h values 36% higher than controls. CONCLUSION: CYP2B6 poor metabolizer genotypes exacerbate the efavirenz-levonorgestrel interaction, likely by increased CYP3A induction with higher efavirenz exposure, making the interaction more difficult to overcome. NAT2 slow acetylator genotypes attenuate the rifampin-levonorgestrel interaction, likely by increased CYP3A inhibition with higher isoniazid exposure.

Mortality rates by gender and sexual orientation reveal a disproportionally high mortality among cisgender men of unknown sexual orientation and men who have sex with women in a cohort of people living with HIV in Rio de Janeiro, Brazil.

BACKGROUND: Antiretroviral therapy use has led to a decline in HIV-related mortality yet disparities by gender and/or sexual orientation may exist. In this study, we estimated hazards of death in people living with HIV (PLWH) according to gender and sexual orientation. METHODS: We included PLWH ≥ 18 years enrolled between 2000 and 2018 at INI/Fiocruz, Rio de Janeiro, Brazil. Participants were grouped as cisgender or transgender women, cisgender men who have sex with men (MSM) or men who have sex with women, or cisgender men with unknown sexual orientation. We assessed disparities in the hazard of death using Cox proportional hazards models. RESULTS: Among 5,576 PLWH, median age at enrollment was 35 years, 39% were MSM, 28% cisgender women, 23% men who have sex with women, 5% transgender women, and 5% men with unknown sexual orientation. A total of 795 deaths occurred in 39,141 person-years of follow-up. Mortality rates per 1,000 person-years were: 82.4 for men with unknown sexual orientation, 24.5 for men who have sex with women, 18.3 for cisgender, 16.6 for transgender women, and 15.1 for MSM. Compared to MSM, men with unknown sexual orientation had the highest death hazard ratio (adjusted hazard ratio [aHR] 2.93, 95% confidence interval [CI] 2.35-3.81), followed by men who have sex with women (aHR 1.17, 95%CI 0.96, 1.43); death hazard ratios for cisgender and transgender women were not statistically different. CONCLUSION: We observed disparities in the hazard of death for men with unknown sexual orientation and men who have sex with women despite universal access to antiretroviral therapy in Brazil. Future work should characterize and assist men with unknown sexual orientation with tailored policies and interventions. Increased hazard of death was not observed for transgender women, which probably results from interventions implemented in our service to reach, engage, retain, and support this population.

Pharmacokinetics of dose-adjusted levonorgestrel emergency contraception combined with efavirenz-based antiretroviral therapy or rifampicin-containing tuberculosis regimens.

OBJECTIVES: To determine if double-dose levonorgestrel emergency contraception (EC) in combination with efavirenz or rifampicin, 2 drugs known to decrease levonorgestrel exposure, resulted in similar pharmacokinetics compared to standard-dose levonorgestrel EC without drug-drug interactions. STUDY DESIGN: We conducted a phase 2, open-label, multicenter, partially randomized, 4 parallel group trial in pre-menopausal females ≥16 years old without an indication for EC and not on hormonal contraception. Participants on dolutegravir-based antiretroviral therapy (ART) received levonorgestrel 1.5 mg (control group); those on rifampicin-containing tuberculosis therapy received levonorgestrel 3 mg; those on efavirenz-based ART were randomized 1:2 to levonorgestrel 1.5 mg or 3 mg. Plasma was collected through 48 hours post-dose to assess levonorgestrel pharmacokinetics. Area under the concentration-time curve (AUC) over 8 hours was the primary outcome. Levonorgestrel pharmacokinetic parameters were compared between groups using geometric mean ratios (GMR) with 90% confidence intervals. RESULTS: The median (Q1, Q3) age for all participants (n = 118) was 34 (27, 41) years and BMI was 23.2 (20, 26.3) kg/m2. Participants receiving levonorgestrel 1.5mg plus efavirenz (n = 17) had 50% lower AUC0-8h compared to the control group (n = 32) [0.50 (0.40, 0.62)]. Participants receiving levonorgestrel 3 mg had a similar AUC0-8h when receiving either efavirenz (n = 35) [0.99 (0.81, 1.20)] or rifampicin (n = 34) [1.16 (0.99, 1.36)] compared to control. Levonorgestrel 3 mg resulted in similar or higher maximum concentration with either efavirenz [1.17 (0.96, 1.41)] or rifampicin [1.27 (1.09, 1.49)] compared to the control group. CONCLUSIONS: Doubling the dose of levonorgestrel EC successfully increased levonorgestrel exposure over the first 8 hours in participants receiving either efavirenz-based ART or rifampicin-containing tuberculosis therapy. IMPLICATIONS: Adjusting levonorgestrel emergency contraception from 1.5 mg to 3 mg improves levonorgestrel pharmacokinetic exposure in participants receiving either efavirenz-based antiretroviral regimens or rifampicin-containing tuberculosis therapy. These data support guideline recommendations to double the dose of levonorgestrel emergency contraception in persons on medications that decrease levonorgestrel exposure by inducing levonorgestrel metabolism.

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.

Travestis, transgender women and young MSM are at high risk for PrEP early loss to follow-up in Rio de Janeiro, Brazil.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (FTC/TDF) is highly effective in preventing HIV infection. This study aimed to identify factors associated with PrEP early loss to follow-up (ELFU) among gay, bisexual and other men who have sex with men (MSM), travestis and transgender women (TGW). METHODOLOGY: This was a prospective cohort study evaluating TGW and MSM who initiated PrEP at the Evandro Chagas National Institute of Infectious Diseases (INI-Fiocruz) from 2014 to 2020. ELFU was defined as not returning for a PrEP visit within 180 days after first dispensation. Exposure variables included age, gender, race, education, transactional sex, condomless anal intercourse [CAI] (both in the past six months), binge drinking and substance use (both in past three months) and syphilis diagnosis at baseline. Multilevel logistic regression models with random intercepts and fixed slopes were used to identify factors associated with ELFU accounting for clustering of participants according to their PrEP initiation study/context (PrEP Brasil, PrEParadas, ImPrEP and PrEP SUS). RESULTS: Among 1,463 participants, the median age was 29 years (interquartile range 24-36), 83% self-identified as MSM, 17% as TGW, 24% were black, 37% mixed-black/pardo and 30% had < 12 years of education. Fifteen percent reported transactional sex, 59% reported CAI, 67% binge drinking, 33% substance use, and 15% had a syphilis diagnosis. Overall, 137 participants (9.7%) had ELFU. Younger age (18-24 years) (adjusted odds ratio [aOR] 1.9, 95%CI:1.2-3.2), TGW (aOR 2.8, 95%CI:1.6-4.8) and education < 12 years (aOR 1.9, 95%CI:1.2-2.9) were associated with greater odds of ELFU. CONCLUSION: TGW, young individuals and those with lower education were at higher risk of PrEP ELFU. Our results suggest that the development of specific strategies targeting these populations should be a priority, through policies that aim to reduce the incidence of HIV infection.

Mortality rates by gender and sexual orientation reveal a disproportionally high mortality among cisgender men of unknown sexual orientation and men who have sex with women in a cohort of people living with HIV in Rio de Janeiro, Brazil

ABSTRACT Background: Antiretroviral therapy use has led to a decline in HIV-related mortality yet disparities by gender and/or sexual orientation may exist. In this study, we estimated hazards of death in people living with HIV (PLWH) according to gender and sexual orientation. Methods: We included PLWH ≥ 18 years enrolled between 2000 and 2018 at INI/Fiocruz, Rio de Janeiro, Brazil. Participants were grouped as cisgender or transgender women, cisgender men who have sex with men (MSM) or men who have sex with women, or cisgender men with unknown sexual orientation. We assessed disparities in the hazard of death using Cox proportional hazards models. Results: Among 5,576 PLWH, median age at enrollment was 35 years, 39% were MSM, 28% cisgender women, 23% men who have sex with women, 5% transgender women, and 5% men with unknown sexual orientation. A total of 795 deaths occurred in 39,141 person-years of follow-up. Mortality rates per 1,000 person-years were: 82.4 for men with unknown sexual orientation, 24.5 for men who have sex with women, 18.3 for cisgender, 16.6 for transgender women, and 15.1 for MSM. Compared to MSM, men with unknown sexual orientation had the highest death hazard ratio (adjusted hazard ratio [aHR] 2.93, 95% confidence interval [CI] 2.35-3.81), followed by men who have sex with women (aHR 1.17, 95%CI 0.96, 1.43); death hazard ratios for cisgender and transgender women were not statistically different. Conclusion: We observed disparities in the hazard of death for men with unknown sexual orientation and men who have sex with women despite universal access to antiretroviral therapy in Brazil. Future work should characterize and assist men with unknown sexual orientation with tailored policies and interventions. Increased hazard of death was not observed for transgender women, which probably results from interventions implemented in our service to reach, engage, retain, and support this population.

Travestis, transgender women and young MSM are at high risk for PrEP early loss to follow-up in Rio de Janeiro, Brazil

Abstract Introduction Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir (FTC/TDF) is highly effective in preventing HIV infection. This study aimed to identify factors associated with PrEP early loss to follow-up (ELFU) among gay, bisexual and other men who have sex with men (MSM), travestis and transgender women (TGW). Methodology This was a prospective cohort study evaluating TGW and MSM who initiated PrEP at the Evandro Chagas National Institute of Infectious Diseases (INI-Fiocruz) from 2014 to 2020. ELFU was defined as not returning for a PrEP visit within 180 days after first dispensation. Exposure variables included age, gender, race, education, transactional sex, condomless anal intercourse [CAI] (both in the past six months), binge drinking and substance use (both in past three months) and syphilis diagnosis at baseline. Multilevel logistic regression models with random intercepts and fixed slopes were used to identify factors associated with ELFU accounting for clustering of participants according to their PrEP initiation study/context (PrEP Brasil, PrEParadas, ImPrEP and PrEP SUS). Results Among 1,463 participants, the median age was 29 years (interquartile range 24-36), 83% self-identified as MSM, 17% as TGW, 24% were black, 37% mixed-black/pardo and 30% had < 12 years of education. Fifteen percent reported transactional sex, 59% reported CAI, 67% binge drinking, 33% substance use, and 15% had a syphilis diagnosis. Overall, 137 participants (9.7%) had ELFU. Younger age (18-24 years) (adjusted odds ratio [aOR] 1.9, 95%CI:1.2-3.2), TGW (aOR 2.8, 95%CI:1.6-4.8) and education < 12 years (aOR 1.9, 95%CI:1.2-2.9) were associated with greater odds of ELFU. Conclusion TGW, young individuals and those with lower education were at higher risk of PrEP ELFU. Our results suggest that the development of specific strategies targeting these populations should be a priority, through policies that aim to reduce the incidence of HIV infection.

Factors associated with long-term HIV pre-exposure prophylaxis engagement and adherence among transgender women in Brazil, Mexico and Peru: results from the ImPrEP study.

INTRODUCTION: The HIV epidemic continues to disproportionately impact Latin-American transgender women (TGW). We assessed factors associated with long-term pre-exposure prophylaxis (PrEP) engagement and adherence among TGW enrolled in the Implementation of PrEP (ImPrEP) study, the largest PrEP demonstration study in Latin America. METHODS: HIV-negative TGW aged ≥18 years reporting 1+eligibility criteria in the 6 months prior to enrolment (e.g. sex partner known to be living with HIV, condomless anal sex [CAS], transactional sex or having a sexually transmitted infection [STI]) who could safely take PrEP were enrolled. Follow-up visits were conducted at 4 weeks and then quarterly. We conducted logistic regression to identify factors associated with long-term PrEP engagement (3+ follow-up visits in 52 weeks) and complete self-reported adherence (no missed pills in the past 30 days) during follow-up. For both outcomes, we constructed multivariable models controlling for country, socio-demographics, sexual behaviour, substance use, STIs and self-reported adherence at 4 weeks (long-term engagement outcome only). RESULTS: From March 2018 to June 2021, ImPrEP screened 519 TGW, enrolled 494 (Brazil: 190, Mexico: 66 and Peru: 238) and followed them for 52 weeks. At baseline, 27.5% of TGW were aged 18-24 years, 67.8% were mixed-race and 31.6% had >secondary education. Most, 89.9% reported CAS, 61.9% had >10 sex partners and 71.9% reported transactional sex. HIV incidence was 1.82 cases per 100 person-years (95% confidence interval [CI]: 0.76-4.38). Almost half of TGW (48.6%) had long-term PrEP engagement, which was positively associated with reporting complete adherence at week 4 (aOR:2.94 [95%CI:1.88-4.63]) and was inversely associated with reporting CAS with unknown-HIV partner (aOR:0.52 [95%CI:0.34-0.81]), migration (aOR:0.54 [95%CI:0.34-0.84]), and being from Mexico (aOR:0.28 [95%CI:0.14-0.53]). Self-reported adherence was associated with TGW aged >34 (aOR:1.61 [95%CI:1.10-2.34]) compared to those aged 25-34 and those with >secondary education (aOR:1.55 [95%CI:1.10-2.19]) and was lower among TGW from Peru (aOR:0.29 [95%CI:0.21-0.41]) or reporting PrEP-related adverse effects (aOR:0.63 [95%CI:0.42-0.92]). CONCLUSIONS: Although TGW were willing to enrol in ImPrEP, long-term PrEP engagement and complete self-reported adherence were limited, and HIV incidence remained relatively high. A successful HIV prevention agenda should include trans-specific interventions supporting oral PrEP and exploring long-acting PrEP strategies for TGW.

Prevalence and predictors of anti-SARS-CoV-2 serology in a highly vulnerable population of Rio de Janeiro: A population-based serosurvey.

Background: COVID-19 serosurveys allow for the monitoring of the level of SARS-CoV-2 transmission and support data-driven decisions. We estimated the seroprevalence of anti-SARS-CoV-2 antibodies in a large favela complex in Rio de Janeiro, Brazil. Methods: A population-based panel study was conducted in Complexo de Manguinhos (16 favelas) with a probabilistic sampling of participants aged ≥1 year who were randomly selected from a census of individuals registered in primary health care clinics that serve the area. Participants answered a structured interview and provided blood samples for serology. Multilevel regression models (with random intercepts to account for participants' favela of residence) were used to assess factors associated with having anti-S IgG antibodies. Secondary analyses estimated seroprevalence using an additional anti-N IgG assay. Findings: 4,033 participants were included (from Sep/2020 to Feb/2021, 22 epidemic weeks), the median age was 39·8 years (IQR:21·8-57·7), 61% were female, 41% were mixed-race (Pardo) and 23% Black. Overall prevalence was 49·0% (95%CI:46·8%-51·2%) which varied across favelas (from 68·3% to 31·4%). Lower prevalence estimates were found when using the anti-N IgG assay. Odds of having anti-S IgG antibodies were highest for young adults, and those reporting larger household size, poor adherence to social distancing and use of public transportation. Interpretation: We found a significantly higher prevalence of anti-S IgG antibodies than initially anticipated. Disparities in estimates obtained using different serological assays highlight the need for cautious interpretation of serosurveys estimates given the heterogeneity of exposure in communities, loss of immunological biomarkers, serological antigen target, and variant-specific test affinity. Funding: Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), the European Union's Horizon 2020 research and innovation programme, Royal Society, Serrapilheira Institute, and FAPESP.

In-hospital mortality and severe outcomes after hospital discharge due to COVID-19: A prospective multicenter study from Brazil.

Background: We evaluated in-hospital mortality and outcomes incidence after hospital discharge due to COVID-19 in a Brazilian multicenter cohort. Methods: This prospective multicenter study (RECOVER-SUS, NCT04807699) included COVID-19 patients hospitalized in public tertiary hospitals in Brazil from June 2020 to March 2021. Clinical assessment and blood samples were performed at hospital admission, with post-hospital discharge remote visits. Hospitalized participants were followed-up until March 31, 2021. The outcomes were in-hospital mortality and incidence of rehospitalization or death after hospital discharge. Kaplan-Meier curves and Cox proportional-hazard models were performed. Findings: 1589 participants [54.5% male, age=62 (IQR 50-70) years; BMI=28.4 (IQR,24.9-32.9) Kg/m² and 51.9% with diabetes] were included. A total of 429 individuals [27.0% (95%CI,24.8-29.2)] died during hospitalization (median time 14 (IQR,9-24) days). Older age [vs<40 years; age=60-69 years-aHR=1.89 (95%CI,1.08-3.32); age=70-79 years-aHR=2.52 (95%CI,1.42-4.45); age≥80-aHR=2.90 (95%CI 1.54-5.47)]; noninvasive or mechanical ventilation at admission [vs facial-mask or none; aHR=1.69 (95%CI 1.30-2.19)]; SAPS-III score≥57 [vs<57; aHR=1.47 (95%CI 1.13-1.92)] and SOFA score≥10 [vs <10; aHR=1.51 (95%CI 1.08-2.10)] were independently associated with in-hospital mortality. A total of 65 individuals [6.7% (95%CI 5.3-8.4)] had a rehospitalization or death [rate=323 (95%CI 250-417) per 1000 person-years] in a median time of 52 (range 1-280) days post-hospital discharge. Age ≥ 60 years [vs <60, aHR=2.13 (95%CI 1.15-3.94)] and SAPS-III ≥57 at admission [vs <57, aHR=2.37 (95%CI 1.22-4.59)] were independently associated with rehospitalization or death after hospital discharge. Interpretation: High in-hospital mortality rates due to COVID-19 were observed and elderly people remained at high risk of rehospitalization and death after hospital discharge. Funding: Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Programa INOVA-FIOCRUZ.

Low PrEP adherence despite high retention among transgender women in Brazil: the PrEParadas study.

INTRODUCTION: We aimed to evaluate daily oral pre-exposure prophylaxis (PrEP) uptake, retention, and adherence and predictors of study non-attendance and low PrEP adherence in a Brazilian trans-specific 48-week study (PrEParadas). METHODS: We enrolled transgender women (TGW) engaging in high-risk sexual behaviours between August 2017 and December 2018. PrEP adherence was based on tenofovir diphosphate concentrations in dried blood spots (DBS). We used random effects logistic regression models and ordinal models to estimate the odds of having a missed visit and of low PrEP adherence, respectively. Multivariable models were adjusted for variables with p-value<0.10 in the univariate analysis. RESULTS: From the 271 eligible, 130 participants were enrolled in the study (PrEP uptake: 48%), out of which 111 (85.4%) were retained at 48 weeks. Multivariable model for study non-attendance included study visit, age, main sexual partner and stimulant use. The odds of missing a visit increased after the week 24. Participants aged 18-24 (adjusted odds ratio [aOR] = 8.76, 95% CI: 2.09-36.7) and 25-34 years (aOR = 6.79, 95% CI: 1.72-26.8) compared to TGW aged 35+ years had significantly higher odds of having a missed visit. The odds of a missed visit were higher among participants reporting stimulant use (aOR = 4.99, 95% CI: 1.37-18.1) compared to no stimulant use. DBS levels at week 48 showed that 42 (38.5%), 14 (12.8%) and 53 (48.6%) of 109 participants had low, moderate and high PrEP adherence. Multivariable model for low PrEP adherence included study visit, age, schooling, race/colour, housing, binge drinking, stimulant use, feminizing hormone therapy (FHT) use and received text message. Low PrEP adherence was significantly higher among participants with less years of schooling (aOR = 6.71, 95% CI: 1.30-34.5) and had a borderline association with Black colour/race (aOR = 6.72, 95% CI: 0.94-47.8). Participants using the FHT available at the site had decreased odds of low PrEP adherence (aOR = 0.38, 95% CI: 0.16-0.88). No participant seroconverted over the course of the study. CONCLUSIONS: Although high PrEP retention can be achieved in a gender-affirming setting, PrEP adherence may be an important challenge faced among TGW due to social disparities. The scale-up of prevention tools like PrEP will have to address systemic social determinants as these stand as important barriers for TGW's access to health services.

Association of Discrimination, Violence, and Resilience with Depressive Symptoms Among Transgender Women in Rio de Janeiro, Brazil: A Cross-Sectional Analysis.

Transgender women experience violence and discrimination that lead to stress responses and contribute to poor mental health. In this analysis of baseline data from Transcendendo, a trans-specific open cohort in Rio de Janeiro, Brazil, we hypothesized that the experience of discrimination and violence would be associated with depressive symptoms and that resilience could mitigate this association. Results showed that prior experiences with discrimination and sexual and physical violence were associated with depressive symptoms, while resilience was inversely associated with depressive symptoms. Resilience did not moderate nor mediate the strong effects of discrimination and violence on depressive symptoms in adjusted models.

Complementary Recruitment Strategies to Reach Men Who Have Sex with Men and Transgender Women: The Experience of a Large Brazilian HIV Prevention Service.

Different strategies have been used to reach men who have sex with men (MSM) and transgender women (TGW) for HIV prevention services. We described the characteristics of MSM and TGW attending a large HIV prevention service in Brazil according to different recruitment strategies or referrals. A total of 2713 individuals (2246[82.8%] MSM and 467[17.2%] TGW) attended the service. Among HIV-negative MSM and TGW, 74.6% and 82.8% were eligible for pre-exposure prophylaxis (PrEP), respectively. PrEP uptake among MSM and TGW was 56.4% and 39.1%, respectively. Participants were mostly referred by peers (43.6%), followed by web-based (24.1%) and venue-based recruitment (16.2%). More young and Black MSM were referred from venue-based recruitment, and web-based strategies more frequently referred MSM with higher education. TGW who were younger and had higher education were more frequently referred from venue-based recruitment. Web-based recruitment failed to reach TGW. Multiple strategies were complementary to reach diverse MSM and TGW populations.

RESUMEN: Diferentes estrategias se han usado para alcanzar hombres que tienen sexo con hombres (HSH) y mujeres trans (MT) en los servicios preventivos del VIH. Describimos las características de HSH y MT que acudieron a un servicio de prevención del VIH en Brasil, de acuerdo con diferentes estrategias de reclutamiento. Un total de 2713 personas (2246[82.8%] HSH y 467[17.2%] MT) asistieron al servicio y aquellos con resultado negativo al VIH (74.6% de HSH y 82.8% de MT) fueron candidatos a la profilaxis preexposición, siendo iniciada por 56.4% y 39.1%, respectivamente. Las referencias al servicio vinieron de pares (43.6%), en línea (24.1%) o por algún sitio (16.2%). Mayoritariamente los HSH jóvenes y negros, y las MT jóvenes con educación superior fueron referidos de algún sitio; mientras que los HSH con educación superior fueron en línea. Este último reclutamiento no sirvió para las MT. Múltiples estrategias fueron complementarias para alcanzar HSH y MT.

High Rates of Sexualized Drug Use or Chemsex among Brazilian Transgender Women and Young Sexual and Gender Minorities.

(1) Background: We aimed to estimate sexualized drug use (SDU) prevalence and its predictors among sexual and gender minorities. (2) Methods: We used an online and on-site survey to enroll sexual/gender minorities people between October-December/2020, and multivariate logistic regression to obtain SDU correlates. (3) Results: We enrolled 3924 individuals (280 transgender women [TGW], 3553 men who have sex with men [MSM], and 91 non-binary), 29.0% currently on pre-exposure prophylaxis (PrEP). SDU prevalence was 28.8% (95% confidence interval [CI] 27.4-30.2). TGW had 2.44-times increased odds (95%CI 1.75-3.39) of engaging in SDU compared to MSM, regardless of PrEP use. PrEP use (aOR 1.19, 95%CI 1.00-1.41), South/Southeast region (aOR 1.26, 95%CI 1.04-1.53), younger age (18-24 years: aOR 1.41, 95%CI 1.10-1.81; 25-35 years: aOR 1.24, 95%CI 1.04-1.53), white race/color (aOR 1.21, 95%CI 1.02-1.42), high income (aOR 1.32, 95%CI 1.05-1.67), binge drinking (aOR 2.66, 95%CI 2.25-3.14), >5 sexual partners (aOR 1.88, 95%CI 1.61-2.21), condomless anal sex (aOR 1.49, 95%CI 1.25-1.79), self-reported sexually transmitted infection (aOR 1.40, 95%CI 1.14-1.71), and higher perceived HIV-risk (aOR 1.37, 95%CI 1.14-1.64) were associated with SDU. (4) Conclusions: TGW had the highest SDU odds. SDU may impact HIV vulnerability among key populations and should be addressed in HIV prevention approaches.

Accelerating adolescent HIV research in low-income and middle-income countries: evidence from a research consortium.

OBJECTIVE: Many adolescents and young adults (AYA) have unmet HIV prevention needs. We describe the Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings (PATC3H) consortium organization, transition milestones, and youth engagement strategies. The PATC3H consortium focuses on reducing HIV incidence and related health disparities among AYA. DESIGN AND METHODS: Organizational data were obtained from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and supplemented with a brief survey completed by study principal investigators. Transition from the initial phase (years 1 and 2) to the subsequent phase (years 3 and 5) was contingent on meeting prespecified milestones. We reviewed the structure and function of the research consortium, identified shared elements of transition milestones, and examined common youth engagement strategies. RESULTS: The PATC3H consortium supports eight research studies through a milestone transition mechanism. The consortium includes AYA HIV research studies in seven countries - Brazil, Kenya, Mozambique, Nigeria, South Africa, Uganda, and Zambia. The NIH request for applications required transition milestones that included early consultation with stakeholders. The transition milestones required by NIH for the eight studies included early consultation with health and policy stakeholders, pilot intervention data, and commitment from national government stakeholders. All studies provided multiple pathways for AYA engagement, including AYA advisory boards and youth-led research studies. CONCLUSION: Data suggest that requiring milestones to transition to the final phase may have facilitated health and policy stakeholder engagement and enhanced formative assessment of regulatory protocols. These data have implications for designing engaged research studies in low and middle-income countries.

Evidence of an untamed HIV epidemic among MSM and TGW in Rio de Janeiro, Brazil: a 2018 to 2020 cross-sectional study using recent infection testing.

INTRODUCTION: Monitoring the HIV epidemic and identifying populations among whom HIV is spreading is critical. We aimed to provide an estimate of the annualized HIV incidence rate using recency testing among cisgender men who have sex with men (MSM) and transgender women (TGW) at a reference centre in Rio de Janeiro, Brazil. METHODS: We evaluated MSM and TGW who sought HIV testing at the Evandro Chagas National Institute of Infectious Diseases-FIOCRUZ between March 2018 and January 2020. The Limiting Avidity assay (LAg) as part of a recent infection testing algorithm (RITA) was employed to identify recent infections (those with a normalized optical density ≤1.5 in the LAg that met all RITA criteria) among those who tested positive for HIV and the annualized HIV incidence was estimated. RESULTS AND DISCUSSION: Out of 3053 individuals assessed, 2591 (84.9%) were HIV negative and 462 (15.1%) were living with HIV. Among these, 302 (65.4%) with stored samples available were evaluated and 73/302 (24.2%) were classified as recent infections. The annualized incidence rate estimate using a false recency rate of zero was 7.35% (95% CI 5.76% to 9.25%). CONCLUSIONS: Our results suggest that the HIV epidemic in Rio de Janeiro, Brazil, continues to disproportionately burden vulnerable populations, including MSM and TGW despite the existence and availability of effective preventive and therapeutic interventions.

High prevalence of anal high-risk HPV infection among transwomen: estimates from a Brazilian RDS study.

INTRODUCTION: As the leading sexually transmitted infection worldwide, human papillomavirus (HPV) may disproportionately affect transwomen. We aimed to estimate anal HPV prevalence, especially focusing on high-risk (hr)-HPV types and evaluate their associated factors among transwomen living in Rio de Janeiro, Brazil. METHODS: Transwomen enrolled in a respondent-driven sampling (RDS)-based survey conducted between August 2015 and January 2016 self-collected anal samples, which were promptly stored at minus 80°C. After DNA extraction, HPV detection and genotyping were performed using the PapilloCheck test. We estimated HPV prevalences and evaluated the correlates of anal hr-HPV infection using a regression logistic model. RESULTS: Out of 345 transwomen, 272 (78.8%) were included in this analysis (122 [44.9%] HIV-positive). No participant had ever received HPV vaccination. Among participants enrolled, 212 (77.9%) were positive for any anal HPV type and 165 (60.7%) for hr-HPV. Most common hr-HPV were as follows: HPV16 (17.6%), HPV68 (14.7%), HPV39 (14.3%), HPV56 (12.5%), HPV51 (11.4%) and HPV52 (11.0%). HIV-positive transwomen had three times the odds of having an hr-HPV compared to HIV-negative transwomen. Participants who had a current rectal Neisseria gonorrhoeae infection had 3.7 times the odds of being coinfected with hr-HPV. Among HIV-positive transwomen, neither antiretroviral therapy use, undetectable viral load, current and nadir CD4 counts were associated with anal hr-HPV infection. CONCLUSIONS: Brazilian transwomen in our study exhibit some of the highest population-specific rates of HPV and hr-HPV. There is an urgent need to elucidate the burden of HPV infection, prevalence of HPV-related diseases and access to and uptake of HPV vaccination among transwomen, especially from low- and middle-income settings.

The Prevalence of HIV Among Men Who Have Sex With Men (MSM) and Young MSM in Latin America and the Caribbean: A Systematic Review.

Young men who have sex with men (YMSM) under 25 years old are among the few populations with increasing numbers of new HIV infections in parts of the world where HIV incidence is declining overall. In this systematic review, we synthesize the literature on HIV prevalence among MSM in Latin America and the Caribbean focusing on YMSM. Results were stratified according to study population sampling method used (probability and non-probability based). Forty-seven studies from 17 countries were published in the last 10 years. Among studies using probability-based sampling method (N = 21), HIV prevalence among MSM ranged from 1.2 to 32.6%. HIV prevalence tended to increase over time in studies sampling at different time points. HIV prevalence among YMSM exceeded 5.0% in more than a half of studies (51%; N = 22/43). Our review corroborates the high and potentially rising incidence of HIV among YMSM and characterizes the region's greatest challenge to ending the epidemic.

RESUMEN: Los hombres jóvenes que tienen sexo con hombres (JHSH) menores de 25 años se encuentran entre las pocas poblaciones con un aumento en las nuevas infecciones por VIH en regiones del mundo donde la incidencia del VIH está disminuyendo en general. En esta revisión sistemática, resumimos la literatura sobre la prevalencia del VIH entre HSH en América Latina y el Caribe, con un enfoque en JHSH. Los resultados se estratificaron por método de muestreo de la población de estudio (probabilístico y no probabilístico). Nuestra investigación encontró 47 estudios de 17 países publicados en los últimos 10 años. Entre los estudios que utilizaron muestreo probabilístico (N = 21), la prevalencia del VIH entre HSH osciló entre 1.2% y 32.6%. La prevalencia del VIH aumentó con el tiempo en ciudades que repitieron el método de muestreo. La prevalencia del VIH entre JHSH superó el 5.0% en más de la mitad de los estudios (51%; N = 22/43). Nuestro análisis corrobora la alta y potencialmente creciente incidencia de VIH entre JHSH y caracteriza el mayor desafío de la región para poner fin a la epidemia.