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.

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

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

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

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

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.

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

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

How heterogeneous are MSM from Brazilian cities? An analysis of sexual behavior and perceived risk and a description of trends in awareness and willingness to use pre-exposure prophylaxis.

BACKGROUND: Brazil has the largest population of individuals living with HIV/AIDS in Latin America, with a disproportional prevalence of infection among gays, bisexuals and other men who have sex with men (MSM). Of relevance to prevention and treatment efforts, Brazilian MSM from different regions may differ in behaviors and risk perception related to HIV. METHODS: We report on MSM living in 29 different cities: 26 Brazilian state capitals, the Federal District and two large cities in São Paulo state assessed in three web-based surveys (2016-2018) advertised on Grindr, Hornet and Facebook. Using logistic regression models, we assessed the association of risk behavior with HIV perceived risk as well as factors associated with high-risk behavior. RESULTS: A total of 16,667 MSM completed the survey. Overall, MSM from the North and Northeast were younger, more black/mixed-black, of lower income and lower education compared to MSM from the South, Southeast and Central-west. Though 17% had never tested for HIV (with higher percentages in the North and Northeast), condomless receptive anal sex (previous 6 months) and high-risk behavior as per HIV Incidence Risk scale for MSM were observed for 41 and 64%, respectively. Sexual behavior and HIV perceived risk had low variability by city and high-risk behavior was strongly associated with high HIV perceived risk. Younger age, being gay/homosexual, having a steady partner, binge drinking, report of sexually transmitted infection (STI) and ever testing for HIV were associated with increased odds of high-risk behavior. Awareness and willingness to use PrEP increased from 2016 to 2018 in most cities. CONCLUSIONS: Overall, MSM socio-demographic characteristics were heterogeneous among Brazilian cities, but similarities were noted among the cities from the same administrative region with a marked exception of the Federal District not following the patterns for the Central-West. Combination HIV prevention is most needed among young men who self-identify as gay/homosexual, report binge drinking or prior STI.

Performance of HIV pre-exposure prophylaxis indirect adherence measures among men who have sex with men and transgender women: Results from the PrEP Brasil Study.

INTRODUCTION: Efficacy of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for PrEP is strongly dependent on the adherence. We examined the concordance between indirect adherence measures and protective drug levels among participants retained through 48 weeks in the PrEP Brasil Study. METHODS: PrEP Brasil was a prospective, multicenter, open-label demonstration project evaluating PrEP provision for men who have sex with men (MSM) and transgender women (TGW) at higher risk for HIV infection within the setting of Brazilian Public Health System. Three indirect adherence measures were obtained at week 48: medication possession ratio (MPR), pill count and self-report (30-days recall). Tenofovir diphosphate (TFV-DP) concentration in Dried Blood Spot (DBS) was measured at week 48. Areas under (AUC) the receiver operating characteristics (ROC) curve were used to evaluate the concordance between achieving protective drug levels (TFV-DP≥700fmol/punch) and the indirect adherence measures. Youden's index and distance to corner were used to determine the optimal cutoff points for each indirect adherence measure. We calculated sensitivity, specificity, negative (NPV) and positive (PPV) predictive values for the found cutoff points. Finally, Delong test was used to compare AUCs. RESULTS AND DISCUSSION: From April, 2014 to July, 2016, 450 participants initiated PrEP, 375(83.3%) were retained through 48 weeks. Of these, 74% (277/375) had TFV-DP ≥700fmol/punch. All adherence measures discriminated between participants with and without protective drug levels (AUC>0.5). High indirect adherence measure was predictive of protective drug levels (PPV>0.8) while low indirect adherence measure was not predictive of lack of protective drug levels (NPV<0.5). No significant differences were found between the adherence methods (p = 0.44). CONCLUSIONS: Low-burden measurements such as MPR and self-report can be used to predict PrEP adherence in a public health context in Brazil for MSM and TGW retained through 48 weeks. Clinical Trial Number: NCT01989611.

High pre-exposure prophylaxis uptake and early adherence among men who have sex with men and transgender women at risk for HIV Infection: the PrEP Brasil demonstration project.

INTRODUCTION: The efficacy of pre-exposure prophylaxis (PrEP) in preventing sexual acquisition of human immunodeficiency virus (HIV) is well established. Little is known about the feasibility of PrEP implementation in middle-income settings with concentrated epidemics among men who have sex with men (MSM) and transgender women (TGW). METHODS: PrEP Brasil is a prospective, multicentre, open-label demonstration project assessing PrEP delivery in the context of the Brazilian Public Health System. HIV-uninfected MSM and TGW in 3 referral centres in Rio de Janeiro and São Paulo were evaluated for eligibility and offered 48 weeks of daily emtricitabine/tenofovir for PrEP. Concentrations of tenofovir diphosphate in dried blood spot samples (DBS) at week 4 after enrolment (early adherence) were measured. Predictors of drug levels were assessed using ordinal logistic regression models considering the DBS drug level as a 3 level variable (<350 fmol/punch, ≥350-699 fmol/punch and ≥700 fmol/punch). RESULTS: 1,270 individuals were assessed for participation; n = 738 were potentially eligible and n = 450 were offered PrEP (PrEP uptake was 60.9%). Eligible but not enrolled individuals were younger, had lower HIV risk perception and had lower PrEP awareness. At week 4, 424 participants (of the 450 enrolled) had DBS TFV-DP concentrations, 94.1% in the protective range (≥350 fmol/punch, consistent with ≥2 pills per week), and 78% were in the highly protective range (≥700 fmol/punch, ≥4 pills per week). Participants with ≥12 years of schooling had 1.9 times the odds (95%CI 1.10-3.29) of a higher versus lower drug level than participants with <12 years of schooling. Condomless receptive anal intercourse in the prior 3 months was also associated with higher drug levels (adjusted OR = 1.78; 95% CI 1.08-2.94). CONCLUSION: The high uptake and early adherence indicate that PrEP for high-risk MSM and TGW can be successfully delivered in the context of the Brazilian Public Health System. Interventions to address disparities on PrEP awareness and HIV risk perception among the younger and less educated are urgently needed in order to maximize the impact of this prevention strategy on the reduction of HIV infection among MSM and TGW in Brazil.

Molecular modeling of a phenyl-amidine class of NMDA receptor antagonists and the rational design of new triazolyl-amidine derivatives.

Recently, many efforts have been made to develop N-methyl-D-aspartic acid receptor antagonists for treating different pathological conditions such as thrombo-embolic stroke, traumatic head injury, Huntington's, Parkinson's, and Alzheimer's diseases). However, as side-effects limit the use of most antagonists, new drugs are still required. In this work, we performed a (quantitative) structure-activity relationship analysis of 17 phenyl-amidine derivatives (1a-1q), reported as N-methyl-D-aspartic acid receptor antagonists, and used this data to rationally design the triazolyl-amidines. The best (quantitative) structure-activity relationship model constructed by multiple linear regression analysis presented high data fitting (R = 0.914) was able to explain 83.6% of the biological data variance (R(2) = 0.836), presented a satisfactory internal predictive ability (Q(2) = 0.609) and contained the descriptors (E(HOMO), Ovality and cLogP). Our assays confirmed that glutamate promotes an extensive cell death in avian neurons (77%) and 2a and 2b protected the neurons from the glutamate effect (from 77% to 27% and 45%, respectively). The results of neurotoxicity and cytotoxicity on Vero cells suggested the favorable profile of 2a and 2b. Also, the molecular modeling used to predict the activity, the interaction with the receptor and the pharmacokinetic and toxicity of the triazolyl-amidines pointed them as a promising class for further exploration as N-methyl-D-aspartic acid receptor antagonists.