Mpox severity and associated hospitalizations among people with HIV and related immunosuppression in Brazil.

OBJECTIVES: This study aimed to analyze characteristics of mpox hospitalization in a Brazilian cohort, further exploring the impact of HIV on mpox-related outcomes and hospitalization. DESIGN: We conducted a descriptive analysis, comparing characteristics of individuals diagnosed with mpox according to hospitalization and HIV status, and described the mpox cases among those living with HIV. METHODS: This was a single-center, prospective cohort study conducted at a major infectious diseases referral center in Rio de Janeiro, Brazil, that enrolled participants older than 18 years of age diagnosed with mpox. Information was collected on standardized forms, including data on sociodemographic, behavioral, clinical and laboratory characteristics. For comparisons, we used chi-squared, Fisher's exact and the Moods median tests whenever appropriate. RESULTS: From June to December, 2022, we enrolled 418 individuals diagnosed with mpox, of whom 52% were people with HIV (PWH). PWH presented more frequently with fever, anogenital lesions and proctitis. The overall hospitalization rate was 10.5% ( n  = 43), especially for pain control. Among hospitalized participants, PWH had more proctitis and required invasive support. Mpox severity was related to poor HIV continuum of care outcomes and low CD4 + cell counts. All deaths ( n  = 2) occurred in PWH with CD4 + less than 50 cells/µl. CONCLUSION: HIV-related immunosuppression likely impacts mpox clinical outcomes. This is of special concern in settings of poor adherence and late presentation to care related to socioeconomic inequalities, such as Brazil. The HIV continuum of care must be taken into account when responding to the mpox outbreak.

Recent HIV infection and annualized HIV incidence rates among sexual and gender minorities in Brazil and Peru (ImPrEP seroincidence study): a cross-sectional, multicenter study.

Background: HIV incidence estimation is critical for monitoring the HIV epidemic dynamics and the effectiveness of public health prevention interventions. We aimed to identify sexual and gender minorities (SGM) with recent HIV infections, factors associated with recent HIV infection, and to estimate annualised HIV incidence rates. Methods: Cross-sectional multicentre study in HIV testing services in Brazil and Peru (15 cities). Inclusion criteria: 18+ years, SGM assigned male at birth, not using pre-/post-exposure prophylaxis. We identified recent HIV infection using the Maxim HIV-1 LAg-Avidity EIA assay as part of a recent infection testing algorithm (RITA). Annualized HIV incidence was calculated using the UNAIDS/WHO incidence estimator tool. Multivariable logistic regression models were used to estimate factors associated with recent HIV infection. Trial registration: NCT05674682. Findings: From 31-Jan-2021 to 29-May-2022, 6899 individuals participated [Brazil: 4586 (66.5%); Peru: 2313 (33.5%)]; 5946 (86.2%) cisgender men, 751 (10.9%) transgender women and 202 (2.9%) non-binary/gender diverse. Median age was 27 (IQR: 23-34) years. HIV prevalence was 11.4% (N = 784/6899); 137 (2.0%) SGM were identified with recent HIV infection. The overall annualized HIV incidence rate was 3.88% (95% CI: 2.86-4.87); Brazil: 2.62% (95% CI: 1.78-3.43); Peru: 6.69% (95% CI: 4.62-8.69). Participants aged 18-24 years had higher odds of recent HIV infection compared to those aged 30+ years in both countries. Interpretation: Our results highlight the significant burden of HIV epidemic among SGM in large urban centres of Brazil and Peru. Public health policies and interventions to increase access to effective HIV prevention methods such as PrEP are urgently needed in Latin America. Funding: Unitaid, WHO (Switzerland), Ministry of Health from Brazil and Peru.

[Association between schooling and mortality rate from dengue in Brazil]. / Associação entre escolaridade e taxa de mortalidade por dengue no Brasil.

Dengue may be associated with individual level variables, such as schooling, increasing the risk of illness. The objective of this study is to analyze the disparities in dengue mortality among the least and the most educated in Brazil, from 2010 to 2018. This is a retrospective ecological study of the differences in the mortality rate due to dengue between the less and the more educated people in Brazil, according to the mortality rates due to general dengue, by age, sex, and Federative Unit (UF). A bootstrap and multiple imputation procedure for the variable schooling was implemented to consider the multilevel structure of the data from each UF over the years. For each aggregate bank generated, a multilevel Poisson model was adjusted. The improvement in the education level of the Brazilian population did not reflect on the decrease in mortality from dengue. There was an increase in the mortality rate from dengue in Brazil and an increase in the difference in mortality rates between less and more educated. Regardless of the imputation process, the results showed higher mortality rates from dengue among the less educated. Low schooling affected younger people more pronouncedly.

A dengue pode estar associada a variáveis de nível individual, como escolaridade, aumentando o risco de adoecimento. O objetivo deste trabalho é analisar as disparidades da mortalidade por dengue entre os menos e mais escolarizados no Brasil entre os anos de 2010 e 2018. Este é um estudo do tipo ecológico retrospectivo das diferenças na taxa de mortalidade por dengue entre menos e mais escolarizados no Brasil, através das taxas de mortalidade por dengue geral, por idade, sexo e Unidade Federativa (UF). Um procedimento de bootstrap e imputação múltipla para a variável escolaridade foram implementados de modo a considerar a estrutura multinível em cada UF dos dados ao longo dos anos. Para cada banco agregado gerado, foi ajustado um modelo de Poisson multinível. A melhoria na escolaridade da população brasileira não refletiu na diminuição da mortalidade por dengue. Houve um aumento na taxa de mortalidade por dengue no Brasil e um crescimento da diferença de taxas de mortalidade entre menos e mais escolarizados. Independentemente do processo de imputação, os resultados mostraram maiores taxas de mortalidade por dengue entre os menos escolarizados. A baixa escolaridade afetou de forma mais pronunciada os mais jovens.

El dengue puede estar asociado a variables de nivel individual como la educación, aumentando el riesgo de enfermarse. El objetivo de este trabajo es analizar las disparidades de la mortalidad por dengue entre las personas con menor y mayor nivel educativo en Brasil entre los años 2010 y 2018. Estudio del tipo ecológico retrospectivo de las diferencias en la tasa de mortalidad por dengue entre las personas con menor y mayor nivel educativo en Brasil, a través de las tasas de mortalidad por dengue general, por edad, género y Unidad Federativa (UF). Se implementó un procedimiento de bootstrap y de imputación múltiple para la variable de educación para considerar la estructura multinivel en cada UF de los datos a lo largo de los años. Para cada banco agregado generado, se ajustó un modelo de Poisson multinivel. La mejora en la educación de la población brasileña no se reflejó en la disminución de la mortalidad por dengue. Hubo un aumento en la tasa de mortalidad por dengue en Brasil y un crecimiento de la diferencia en las tasas de mortalidad entre las personas con menor y mayor nivel educativo. Independientemente del proceso de imputación, los resultados mostraron mayores tasas de mortalidad por dengue entre los menos educados. El bajo nivel de educación afectó de forma más pronunciada a los más jóvenes.

Immunogenicity and reactogenicity of yellow fever vaccine in people with HIV.

OBJECTIVE: To evaluate immunogenicity and reactogenicity of yellow fever (YF) vaccine in people with HIV (PWH) compared to HIV-uninfected controls. DESIGN: In this longitudinal interventional trial (NCT03132311), PWH with CD4 + cell count ≥200 cells/µl and controls, aged 18-59, without a previous history of YF vaccination received a single standard dose of YF vaccine (17DD) and were followed at Days 5, 30 and Year 1. METHODS: YF-neutralization titers were measured at Days 0, 30 and Year 1 and geometric mean titers (GMT) were calculated. Adverse events (AE) and YF virus detection were measured at Days 5 and 30. Linear regression evaluated factors associated with YF-neutralization titers. RESULTS: Two hundred and eighteen PWH and 82 controls were included. At baseline, all PWH were using antiretroviral therapy; 92.6% had undetectable HIV viral load (VL) and median CD4 + cell count was 630 cells/µl [interquartile range (IQR) 463-888]. YF vaccine was safe and there were no serious AEs. At Day 30, seroconversion was observed in 98.6% of PWH [95% confidence interval (CI): 95.6-99.6] and in 100% of controls (95% CI: 93.9-100); at Year 1, 94.0% of PWH (95% CI: 89.6-96.7) and 98.4% of controls (95% CI 90.3-99.9) were seropositive. PWH had lower GMTs than controls at Day 30 and Year 1. Baseline VL >1000 copies/ml, low CD4 + cell count and low CD4 + /CD8 + ratio were associated with lower YF-neutralization titers. CONCLUSIONS: YF vaccine is safe in PWH with CD4 + cell count ≥200 cells/µl. YF vaccine immunogenicity is impaired in PWH, particularly among those with high VL, low CD4 + cell count and low CD4 + /CD8 + ratio at vaccination and YF-neutralization titers decays over time.

Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil.

BACKGROUND: The increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil. METHODS: Cross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy. RESULTS: A total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4-54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2-17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2-52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy. CONCLUSIONS: We found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients' therapeutic regimens should be implemented.

Long-Acting Injectable Cabotegravir for HIV Preexposure Prophylaxis Among Sexual and Gender Minorities: Protocol for an Implementation Study.

BACKGROUND: Long-acting injectable cabotegravir (CAB-LA) for preexposure prophylaxis (PrEP) has proven efficacious in randomized controlled trials. Further research is critical to evaluate its effectiveness in real-world settings and identify effective implementation approaches, especially among young sexual and gender minorities (SGMs). OBJECTIVE: ImPrEP CAB Brasil is an implementation study aiming to generate critical evidence on the feasibility, acceptability, and effectiveness of incorporating CAB-LA into the existing public health oral PrEP services in 6 Brazilian cities. It will also evaluate a mobile health (mHealth) education and decision support tool, digital injection appointment reminders, and the facilitators of and barriers to integrating CAB-LA into the existing services. METHODS: This type-2 hybrid implementation-effectiveness study includes formative work, qualitative assessments, and clinical steps 1 to 4. For formative work, we will use participatory design methods to develop an initial CAB-LA implementation package and process mapping at each site to facilitate optimal client flow. SGMs aged 18 to 30 years arriving at a study clinic interested in PrEP (naive) will be invited for step 1. Individuals who tested HIV negative will receive mHealth intervention and standard of care (SOC) counseling or SOC for PrEP choice (oral or CAB-LA). Participants interested in CAB-LA will be invited for step 2, and those with undetectable HIV viral load will receive same-day CAB-LA injection and will be randomized to receive digital appointment reminders or SOC. Clinical appointments and CAB-LA injection are scheduled after 1 month and every 2 months thereafter (25-month follow-up). Participants will be invited to a 1-year follow-up to step 3 if they decide to change to oral PrEP or discontinue CAB-LA and to step 4 if diagnosed with HIV during the study. Outcomes of interest include PrEP acceptability, choice, effectiveness, implementation, and feasibility. HIV incidence in the CAB-LA cohort (n=1200) will be compared with that in a similar oral PrEP cohort from the public health system. The effectiveness of the mHealth and digital interventions will be assessed using interrupted time series analysis and logistic mixed models, respectively. RESULTS: During the third and fourth quarters of 2022, we obtained regulatory approvals; programmed data entry and management systems; trained sites; and performed community consultancy and formative work. Study enrollment is programmed for the second quarter of 2023. CONCLUSIONS: ImPrEP CAB Brasil is the first study to evaluate CAB-LA PrEP implementation in Latin America, one of the regions where PrEP scale-up is most needed. This study will be fundamental to designing programmatic strategies for implementing and scaling up feasible, equitable, cost-effective, sustainable, and comprehensive alternatives for PrEP programs. It will also contribute to maximizing the impact of a public health approach to reducing HIV incidence among SGMs in Brazil and other countries in the Global South. TRIAL REGISTRATION: Clinicaltrials.gov NCT05515770; https://clinicaltrials.gov/ct2/show/NCT05515770. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44961.

A Peer-Led Digital Intervention to Reduce HIV Prevention and Care Disparities Among Young Brazilian Transgender Women (The BeT Study): Protocol for an Intervention Study.

BACKGROUND: The HIV epidemic continues to disproportionately burden marginalized populations despite the availability of effective preventive and therapeutic interventions. Transgender women are severely affected by HIV worldwide including in Brazil and other low- and middle-income countries, with evidence of increasing new infections among young people. There is an urgent need for youth-specific HIV prevention and care interventions for young transgender women in Brazil. OBJECTIVE: This study aims to (1) address stigma in the Brazilian public health system and (2) reduce barriers to HIV care and prevention with systems navigation among young transgender women aged 18-24 years in Rio de Janeiro, Brazil. METHODS: The Brilhar e Transcender (BeT) study is a status-neutral, peer-led, single-arm digital intervention study enrolling 150 young transgender women in Rio de Janeiro, Brazil. The intervention was pilot tested and refined using data from a formative phase. The BeT intervention takes place over 3 months, is delivered remotely via mobile phone and in person by peers, and comprises three components: (1) BeT sessions, (2) digital interactions, and (3) automated messages. Eligibility criteria include identifying as transgender women, being aged 18-24 years, speaking in Portuguese, and living in the Rio de Janeiro metropolitan area in Brazil. The primary outcomes are HIV incidence, pre-exposure prophylaxis uptake, linkage to HIV care, and viral suppression. Primary outcomes were assessed at baseline and quarterly for 12 months. Participants respond to interviewer-based surveys and receive tests for HIV and sexually transmitted infections. RESULTS: The study has been approved by the Brazilian and the US local institutional review boards in accordance with all applicable regulations. Study recruitment began in February 2022 and was completed in early July 2022. Plans are to complete the follow-up assessment of study participants on July 2023, analyze the study data, and disseminate intervention results by December 2023. CONCLUSIONS: Interventions to engage a new generation of transgender women in HIV prevention and care are needed to curb the epidemic. The BeT study will evaluate a digital peer-led intervention for young transgender women in Brazil, which builds on ways young people engage in systems and uses peer-led support to empower transgender youth in self-care and health promotion. A promising evaluation of the BeT intervention may lead to the availability of this rapidly scalable status-neutral HIV intervention that can be translated throughout Brazil and other low- and middle-income countries for young transgender women at high risk of or living with HIV. TRIAL REGISTRATION: ClinicalTrials.gov NCT05299645; https://clinicaltrials.gov/ct2/show/NCT05299645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44157.

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.

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.

Same-day initiation of oral pre-exposure prophylaxis among gay, bisexual, and other cisgender men who have sex with men and transgender women in Brazil, Mexico, and Peru (ImPrEP): a prospective, single-arm, open-label, multicentre implementation study.

BACKGROUND: Although gay, bisexual, and other cisgender men who have sex with men (MSM) and transgender women have the highest HIV burden in Latin America, pre-exposure prophylaxis (PrEP) implementation is poor. We aimed to assess the feasibility of same-day oral PrEP delivery in Brazil, Mexico, and Peru. METHODS: Implementation PrEP (ImPrEP) was a prospective, single-arm, open-label, multicentre PrEP implementation study conducted in Brazil (14 sites), Mexico (four sites), and Peru (ten sites). MSM and transgender women were eligible to participate if they were aged 18 years or older, HIV-negative, and reported one or more prespecified criteria. Enrolled participants received same-day initiation of daily oral PrEP (tenofovir disoproxil fumarate [300 mg] coformulated with emtricitabine [200 mg]). Follow-up visits were scheduled at week 4 and quarterly thereafter. We used logistic regression models to identify factors associated with early loss to follow-up (not returning after enrolment), PrEP adherence (medication possession ratio ≥0·6), and long-term PrEP engagement (attending three or more visits within 52 weeks). This study is registered at the Brazilian Registry of Clinical Trials, U1111-1217-6021. FINDINGS: From Feb 6, 2018, to June 30, 2021, 9979 participants were screened and 9509 were enrolled (Brazil n=3928, Mexico n=3288, and Peru n=2293). 543 (5·7%) participants were transgender women, 8966 (94·3%) were cisgender men, and 2481 (26·1%) were aged 18-24 years. There were 12 185·25 person-years of follow-up. 795 (8·4%) of 9509 participants had early loss to follow-up, 6477 (68·1%) of 9509 were adherent to PrEP, and 5783 (70·3%) of 8225 had long-term PrEP engagement. Transgender women (adjusted odds ratio 1·60, 95% CI 1·20-2·14), participants aged 18-24 years (1·80, 1·49-2·18), and participants with primary education (2·18, 1·29-3·68) had increased odds of early loss to follow-up. Transgender women (0·56, 0·46-0·70), participants aged 18-24 years (0·52, 0·46-0·58), and those with primary education (0·60, 0·40-0·91) had lower odds of PrEP adherence. Transgender women (0·56, 0·45-0·71), participants aged 18-24 years (0·56, 0·49-0·64), and those with secondary education (0·74, 0·68-0·86) had lower odds of long-term PrEP engagement. HIV incidence was 0·85 per 100 person-years (95% CI 0·70-1·03) and was higher for transgender women, participants from Peru, those aged 18-24 years, Black and mixed-race participants, and participants who were non-adherent to PrEP. INTERPRETATION: Same-day oral PrEP is feasible for MSM and transgender women in Latin America. Social and structural determinants of HIV vulnerability need to be addressed to fully achieve the benefits of PrEP. FUNDING: Unitaid, WHO, and Ministries of Health in Brazil, Mexico, and Peru. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

Associação entre escolaridade e taxa de mortalidade por dengue no Brasil / Association between schooling and mortality rate from dengue in Brazil / Asociación entre educación y tasa de mortalidad por dengue en Brasil

A dengue pode estar associada a variáveis de nível individual, como escolaridade, aumentando o risco de adoecimento. O objetivo deste trabalho é analisar as disparidades da mortalidade por dengue entre os menos e mais escolarizados no Brasil entre os anos de 2010 e 2018. Este é um estudo do tipo ecológico retrospectivo das diferenças na taxa de mortalidade por dengue entre menos e mais escolarizados no Brasil, através das taxas de mortalidade por dengue geral, por idade, sexo e Unidade Federativa (UF). Um procedimento de bootstrap e imputação múltipla para a variável escolaridade foram implementados de modo a considerar a estrutura multinível em cada UF dos dados ao longo dos anos. Para cada banco agregado gerado, foi ajustado um modelo de Poisson multinível. A melhoria na escolaridade da população brasileira não refletiu na diminuição da mortalidade por dengue. Houve um aumento na taxa de mortalidade por dengue no Brasil e um crescimento da diferença de taxas de mortalidade entre menos e mais escolarizados. Independentemente do processo de imputação, os resultados mostraram maiores taxas de mortalidade por dengue entre os menos escolarizados. A baixa escolaridade afetou de forma mais pronunciada os mais jovens.

Dengue may be associated with individual level variables, such as schooling, increasing the risk of illness. The objective of this study is to analyze the disparities in dengue mortality among the least and the most educated in Brazil, from 2010 to 2018. This is a retrospective ecological study of the differences in the mortality rate due to dengue between the less and the more educated people in Brazil, according to the mortality rates due to general dengue, by age, sex, and Federative Unit (UF). A bootstrap and multiple imputation procedure for the variable schooling was implemented to consider the multilevel structure of the data from each UF over the years. For each aggregate bank generated, a multilevel Poisson model was adjusted. The improvement in the education level of the Brazilian population did not reflect on the decrease in mortality from dengue. There was an increase in the mortality rate from dengue in Brazil and an increase in the difference in mortality rates between less and more educated. Regardless of the imputation process, the results showed higher mortality rates from dengue among the less educated. Low schooling affected younger people more pronouncedly.

El dengue puede estar asociado a variables de nivel individual como la educación, aumentando el riesgo de enfermarse. El objetivo de este trabajo es analizar las disparidades de la mortalidad por dengue entre las personas con menor y mayor nivel educativo en Brasil entre los años 2010 y 2018. Estudio del tipo ecológico retrospectivo de las diferencias en la tasa de mortalidad por dengue entre las personas con menor y mayor nivel educativo en Brasil, a través de las tasas de mortalidad por dengue general, por edad, género y Unidad Federativa (UF). Se implementó un procedimiento de bootstrap y de imputación múltiple para la variable de educación para considerar la estructura multinivel en cada UF de los datos a lo largo de los años. Para cada banco agregado generado, se ajustó un modelo de Poisson multinivel. La mejora en la educación de la población brasileña no se reflejó en la disminución de la mortalidad por dengue. Hubo un aumento en la tasa de mortalidad por dengue en Brasil y un crecimiento de la diferencia en las tasas de mortalidad entre las personas con menor y mayor nivel educativo. Independientemente del proceso de imputación, los resultados mostraron mayores tasas de mortalidad por dengue entre los menos educados. El bajo nivel de educación afectó de forma más pronunciada a los más jóvenes.

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.

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.

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.

Kidney function and daily emtricitabine/tenofovir disoproxil fumarate pre-exposure prophylaxis against HIV: results from the real-life multicentric demonstrative project PrEP Brazil.

BACKGROUND: Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in the reduction of sexually transmitted HIV infections. The prolonged use of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) co-formulation (TDF/FTC), however, may result in augmented risk of renal toxicity. We aimed to evaluate changes in the estimated Glomerular Filtration Rate (eGFR) in a real-world population setting of participants enrolled in PrEP Brazil, a 48-week prospective, open-label, demonstration study to assess the feasibility of daily oral TDF/FTC used by men who have sex with men and transgender women at high-risk of HIV infection, all over 18 years old. METHODS: Kidney function was assessed by serial measurement of serum creatinine and eGFR with the Modification of Diet in Renal Disease Study (MDRD) formula on weeks 4, 12, 24, 36 and 48. Adherence to PrEP was assessed by dosing TDF concentration in dried blood spots at weeks 4 and 48, measured by liquid chromatography-mass spectrometry or mass spectrometry. RESULTS: Of 392 participants completing the 48-week follow-up protocol with TDF blood detectable levels and eGFR measures, 43.1% were young adults, of Caucasian ethnic background (57.9%), with BMI below 30 kg/m2, without arterial hypertension. At screening, median eGFR was 93.0 mL/min/1.73 m2. At week 4 follow-up, 90 (23% of the study population) participants presented reductions in eGFR greater than 10 mL/min/1.73 m2 as compared to baseline eGFR, some as large as 59 mL/min/1.73 m2, but with no clinical outcomes (adverse events and renal adverse events) severe enough to demand TDF/FTC discontinuation. A negative relationship was observed between TDF blood levels and eGFR at weeks 4 (r = - 0.005; p < 0.01) and 48 (r = - 0.006; p < 0.01). CONCLUSIONS: These results suggest that the renal function profile in individuals on TDF/FTC may be assessed on week 4 and then only annually, allowing a more flexible medical follow-up in primary care centers.

Interpersonal Violence and Passing: Results from a Brazilian Trans-specific Cross-sectional Study.

Trans women are specifically vulnerable to interpersonal violence. Being perceived as the gender that a transgender person identifies with, defined in some contexts as passing, may influence violence ratings. The EVAS (Violence and Health Self-Evaluation) study was a cross-sectional study that enrolled 121 trans women between 2019 and 2020 in Rio de Janeiro, Brazil, aiming to investigate the association between self-reported passing and different types of interpersonal violence. We enrolled 121 participants who had a median age of 36.3 (interquartile range [IQR] 13.7). Most of them were Black/mixed (78.5%) and had at least a high school education (63%). Most participants considered themselves as trans women (71.9%). Their median monthly income was $252.50 (IQR $302.50). Only 40 (33.1%) trans women had a main partner. Trans women with high passing had a higher prevalence of family violence and lower prevalence of observed police violence, violence in open and closed public spaces. Participants that reported a high passing had higher prevalence of family violence (p = .016); moreover, they reported observing less frequently police violence in the neighborhood they lived in for the last 12 months (p = .012) as well as having lower rates of suffering violence. Trans women who reported high passing had 81% (56%-92%) lower chance of suffering violence in open public places more than once, while prior racism experience had a positive association with violence in an open public place (aOR = 3.93, 95% CI [.48, 15.40]). Passing seems to protect from violence in public spaces, whilst it increases family violence. Data also suggest that observing police violence and violence in close public spaces. There is an urgent need to better understand the complex relationships around violence and foster its prevention.