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.

Cryptococcal Meningitis and Clinical Outcomes in Persons With Human Immunodeficiency Virus: A Global View.

BACKGROUND: Cryptococcal meningitis (CM) is a major cause of morbidity and mortality in persons with human immunodeficiency virus (HIV; PWH). Little is known about CM outcomes and availability of diagnostic and treatment modalities globally. METHODS: In this retrospective cohort study, we investigated CM incidence and all-cause mortality in PWH in the International Epidemiology Databases to Evaluate AIDS cohort from 1996 to 2017. We estimated incidence using quasi-Poisson models adjusted for sex, age, calendar year, CD4 cell count (CD4), and antiretroviral therapy (ART) status. Mortality after CM diagnosis was examined using multivariable Cox models. A site survey from 2017 assessed availability of CM diagnostic and treatment modalities. RESULTS: Among 518 852 PWH, there were 3857 cases of CM with an estimated incidence of 1.54 per 1000 person-years. Mortality over a median of 2.6 years of post-CM diagnosis follow-up was 31.6%, with 29% lost to follow-up. In total, 2478 (64%) were diagnosed with CM after ART start with a median of 253 days from ART start to CM diagnosis. Older age (hazard [HR], 1.31 for 50 vs 35 years), lower CD4 (HR, 1.15 for 200 vs 350 cells/mm3), and earlier year of CM diagnosis (HR, 0.51 for 2015 vs 2000) were associated with higher mortality. Of 89 sites, 34% reported access to amphotericin B; 12% had access to flucytosine. CONCLUSIONS: Mortality after CM diagnosis was high. A substantial portion of CM cases occurred after ART start, though incidence and mortality may be higher than reported due to ascertainment bias. Many sites lacked access to recommended CM treatment.

Acceptability and usability of oral fluid HCV self-testing for hepatitis C diagnosis: A systematic review and meta-analysis.

Data on the acceptability and usability of hepatitis C virus self-testing (HCVST) remain scarce. We estimated the pooled rates of acceptability/feasibility and re-reading/re-testing agreement of HCVST using oral fluid tests (PROSPERO-CRD42022349874). We searched online databases for studies that evaluated acceptability, usability and inter-reader/operator variability for HCVST using oral fluid tests. Pooled estimates of feasibility, agreement and post-testing perspectives were analysed. Sensitivity analyses were performed in men who have sex with men (MSM) and people who inject drugs (PWID). Heterogeneity was assessed using the I2 statistics. A total of six studies comprising 870 participants were identified: USA (n = 95 with liver disease), Kenya (n = 150 PWID), Egypt (n = 116 from the general population), Vietnam (n = 104 MSM and n = 105 PWID), China (n = 100 MSM) and Georgia (n = 100 MSM and n = 100 PWID)]. All studies used OraQuick® HCV Rapid Antibody Test. The pooled overall estimates for correct sample collection and for people who performed HCVST without needing assistance in any step (95% confidence interval [CI]) were 87.2% [76.0-95.3] (n = 755; I2 = 93.7%) and 62.6% [37.2-84.8] (n = 755; I2 = 98.0%), respectively. The pooled estimate of agreement for re-reading was 95.0% [95% CI 91.5-97.6] (n = 831; I2 = 74.0%) and for re-testing was 94.4% [90.3-97.5] (n = 726; I2 = 77.1%). The pooled estimate of those who would recommend HCVST was 94.4% [84.7-99.6] (n = 625; I2 = 93.7%). Pooled estimates (95% CI) of correct sample collection (72.8% [63.3-81.5] vs. 90.8% [85.9-94.8]) and performance of HCVST without needing assistance (44.1% [14.1-76.7] vs. 78.1% [53.4-95.3]) was lower in PWID compared to MSM. In summary, HCV testing with oral fluid HCVST was feasible and well-accepted. Oral fluid HCVST should be considered in key populations for uptake HCV testing.

HIV Risk Perception and Pre-Exposure Prophylaxis (PrEP) Awareness Among Transgender Women from Mexico.

This study aimed to identify factors associated with HIV risk perception among Mexican transgender women (TGW). This cross-sectional survey was conducted online and at a public HIV clinic in Mexico City. Participants were ≥ 18 years old, self-identified as TGW, and reported not living with HIV. They answered questions on sexual behavior, HIV risk perception, and pre-exposure prophylaxis (PrEP) awareness. We performed a multivariate logistic regression to accomplish the study's objective. One hundred ninety-one TGW completed the survey. High HIV risk perception was associated with > 5 sexual partners, condomless receptive anal sex, sex with a male partner(s) of unknown HIV status, and PrEP awareness. Although most TGW reported low HIV risk perception, over half had risk sexual behavior, reflecting inaccurate risk assessment. Future interventions to improve accurate risk perception among TGW should promote HIV transmission and prevention knowledge and increase PrEP awareness and uptake.

RESUMEN: Este estudio tuvo como objetivo identificar los factores asociados con la percepción de riesgo al VIH entre las mujeres trans (MT) mexicanas. El reclutamiento de esta encuesta transversal se realizó en línea y en una clínica pública de VIH en la Ciudad de México. Las participantes tenían ≥ 18 años, se autoidentificaron como MT y reportaron no vivir con VIH. Respondieron preguntas sobre su comportamiento sexual, percepción del riesgo al VIH y conocimiento de la profilaxis preexposición (PrEP). Se realizó un análisis de regresión logística multivariado para cumplir con el objetivo del estudio. Ciento noventa y uno participantes completaron la encuesta. La percepción de alto riesgo al VIH se asoció con > 5 parejas sexuales, sexo anal receptivo sin condón, sexo con una pareja masculina de estado serológico desconocido y conocimiento de la PrEP. Aunque la mayoría de las MT informaron baja percepción del riesgo al VIH, más de la mitad reportaron conductas sexuales de riesgo, lo que refleja una evaluación de riesgo inexacta. Futuras intervenciones para mejorar la percepción precisa del riesgo entre las MT deben centrarse en promover el conocimiento de transmisión y la prevención del VIH, así como aumentar el conocimiento y la aceptación de la PrEP.

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.

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.

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.

Ongoing HIV-1 evolution and reservoir reseeding in two elite controllers with genetically diverse peripheral proviral quasispecies.

BACKGROUND: Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small HIV-1 reservoir composed of identical proviral sequences maintained by clonal expansion of infected CD4+ T cells. However, some have a more diverse peripheral blood mononuclear cell (PBMC)-associated HIV-1 reservoir with unique sequences. OBJECTIVES: To understand the turnover dynamics of the PBMC-associated viral quasispecies in ECs with relatively diverse circulating proviral reservoirs. METHODS: We performed single genome amplification of the env gene at three time points during six years in two EC with high intra-host HIV DNA diversity. FINDINGS: Both EC displayed quite diverse PBMCs-associated viral quasispecies (mean env diversity = 1.9-4.1%) across all time-points comprising both identical proviruses that are probably clonally expanded and unique proviruses with evidence of ongoing evolution. HIV-1 env glycosylation pattern suggests that ancestral and evolving proviruses may display different phenotypes of resistance to broadly neutralising antibodies consistent with persistent immune pressure. Evolving viruses may progressively replace the ancestral ones or may remain as minor variants in the circulating proviral population. MAIN CONCLUSIONS: These findings support that the high intra-host HIV-1 diversity of some EC resulted from long-term persistence of archival proviruses combined with the continuous reservoir's reseeding and low, but measurable, viral evolution despite undetectable viremia.

Monkeypox (Mpox) virus isolation and ultrastructural characterisation from a Brazilian human sample case.

BACKGROUND: According to the last 2023 Monkeypox (Mpox) Outbreak Global Map from the Centres for Disease Control and Prevention (CDC), more than 100 countries with no Mpox infection report cases. Brazil stands out in this group and is the second country with the highest number of cases in the last outbreak. OBJECTIVE: To contribute to knowledge of the virus infection effects in a cellular model, which is important for diagnosis infections not yet included in a provider´s differential diagnosis and for developing viral inhibition strategies. METHODS: We describe a virus isolation protocol for a human clinical sample from a patient from Brazil, the viral growth in a cell model through plaque forming units (PFU) assay, reverse transcriptase polymerase chain reaction (RT-PCR) and transmission electron microscopy (TEM). FINDINGS: We follow the viral isolation in Vero cell culture from a Mpox positive clinically diagnosed sample and show the infection effects on cellular structures using a TEM. MAIN CONCLUSIONS: Understanding the impact of viral growth on cellular structures and its replication kinetics may offer better strategies for the development of new drugs with antiviral properties.

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.

Impact of feminizing hormone therapy on tenofovir and emtricitabine plasma pharmacokinetics: a nested drug-drug interaction study in a cohort of Brazilian transgender women using HIV pre-exposure prophylaxis.

OBJECTIVES: Potential interactions between feminizing hormone therapy (FHT) and pre-exposure prophylaxis (PrEP) may be a barrier to PrEP use among transgender women (TGW). We aimed to assess the impact of FHT on PrEP plasma pharmacokinetics (PK) among TGW. METHODS: This was a PK substudy of the effects of FHT on tenofovir disoproxil fumarate/emtricitabine nested to a trans-specific PrEP demonstration study (NCT03220152). Participants were assigned to receive PrEP only (noFHT) or standardized FHT (sFHT; oestradiol valerate 2-6 mg plus spironolactone 100-300 mg) plus PrEP for 12 weeks, after which they could start any FHT (aFHT). Short- and long-term PK assessment occurred at Weeks 12 and 30-48, respectively (plasma samples prior and 0.5, 1, 2, 4, 6, 8 and 24 h after dose). Non-compartmental PK parameters of tenofovir and emtricitabine were compared as geometric mean ratios (GMRs) between noFHT and PrEP and FHT (sFHT at short-term PK; aFHT at long-term PK) participants. RESULTS: No differences in tenofovir and emtricitabine plasma PK parameters were observed between the short-term PK of noFHT (n = 12) and sFHT participants (n = 18), except for emtricitabine Cmax [GMR: 1.15 (95% CI: 1.01-1.32)], or between noFHT short-term PK and aFHT long-term PK (n = 13). Most participants were on oestradiol valerate 2 mg at the short-term PK (56%) and 4 mg at the long-term PK (54%). Median (IQR) oestradiol levels were 56.8 (43.2-65.4) pg/mL at short-term PK (sFHT) and 44.8 (24.70-57.30) pg/mL at long-term PK (aFHT). No participants in this analysis seroconverted during the study. CONCLUSIONS: Our results indicate no interaction of FHT on tenofovir levels, further supporting PrEP use among TGW using FHT.

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.

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.

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.

Tuberculosis treatment intermittency in the continuation phase and mortality in HIV-positive persons receiving antiretroviral therapy.

BACKGROUND: Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described. METHODS: We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation. RESULTS: 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5-7 days/week and 300(13%) 2-3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5-7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (HR = 0.68; 95% CI = 0.51-0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5-7 days/week vs. 2-3 days/week (HR 0.75, 95%CI 0.55-1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83-2.45; P = 0.20). CONCLUSIONS: TB treatment 5-7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.

Awareness, knowledge, and attitudes related to HIV pre-exposure prophylaxis and other prevention strategies among physicians from Brazil and Mexico: cross-sectional web-based survey.

BACKGROUND: In order to end the HIV epidemic by 2030, combination HIV prevention including pre-exposure prophylaxis (PrEP) should be widely available, especially for the most vulnerable populations. In Latin America and the Caribbean (LAC), only 14 out of 46 countries have access to PrEP. In Brazil and Mexico, PrEP has been provided at no cost through the Public Health System since 2017 and 2021, respectively. Thus, HIV physicians' perspectives about PrEP and other prevention strategies may differ. This study aimed to compare awareness, knowledge, and attitudes related to PrEP and other prevention strategies among HIV physicians from Brazil and Mexico. METHODS: Cross-sectional, web-based survey targeting physicians who prescribe antiretrovirals from both countries. Participants answered questions on socio-demographic, medical experience, awareness, knowledge, and attitudes towards PrEP and other HIV prevention strategies. We stratified all variables per country and compared frequencies using Chi-square, Fisher exact, and Wilcoxon-Mann-Whitney tests, as appropriate. RESULTS: From January-October 2020, 481 HIV physicians were included: 339(70.5%) from Brazil, 276(57.4%) male, and median age was 43 years (IQR = 36-53). Awareness of PrEP did not differ between Brazil and Mexico (84.6%), while awareness of other prevention strategies, including post-exposure prophylaxis and new PrEP technologies, was higher in Brazil. More Brazilians perceived U=U as completely accurate compared to Mexicans (74.0% vs. 62.0%, P < .001). Willingness to prescribe PrEP was 74.2%, higher among Brazilians (78.2%, P = .01). Overall, participants had concerns about consistent access to PrEP medication and the risk of antiretroviral resistance in case of acute HIV infection or seroconversion. The main barriers reported were assumptions that users could have low PrEP knowledge (62.0%) or limited capacity for adherence (59.0%). Compared to Brazilians, Mexicans reported more concerns and barriers to PrEP prescription (all; P ≤ .05), except for consistent access to PrEP medication and the lack of professionals to prescribe PrEP (both; P ≤ .01). CONCLUSIONS: Although awareness of PrEP was similar in Brazil and Mexico, differences in knowledge and attitudes may reflect the availability and stage of PrEP implementation in these countries. Strengthening and increasing information on PrEP technologies and other HIV prevention strategies among HIV physicians could improve their comfort to prescribe these strategies and facilitate their scale-up in LAC.

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.

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.

Impact of COVID-19 Pandemic on Sexual Minority Populations in Brazil: An Analysis of Social/Racial Disparities in Maintaining Social Distancing and a Description of Sexual Behavior.

We conducted a web-based survey to understand the impact of social distancing measures on Brazilian MSM and transgender/non-binary lives. A total of 3486 respondents were included in this analysis and the great majority were cismen (98%). The median age was 32 years (IQR: 27-40), 44% non-white, 36% low schooling and 38% low income. Most of participants reported HIV negative/unknown status (77%). Participants on-PrEP reported more condomless anal sex than those off-PrEP. Conversely, 24% off-PrEP were at substantial HIV-risk. PrEP/ART continuation were reported by the majority, despite reports of impediments to medication refill. Transgender/non-binary reported more mental health problems and challenges to access health care. Social and racial disparities were associated with unattainability of maintaining social distancing. Tailored social and economic support policies during COVID-19 pandemic should be made available to these populations. Challenges for PrEP/ART access will demand the implementation of innovative solutions to avoid the expansion of the HIV epidemic.