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To evaluate the adherence, safety, and feasibility of pre-exposure prophylaxis (PrEP) in real-world settings among adolescent men who have sex with men (AMSM) and transgender women (ATGW). PrEP1519 is a single-arm, multicentric demonstration cohort study of daily oral PrEP among AMSM and ATGW aged 15 to 19 years in Brazil. Study visits occurred at baseline, weeks 4, 12, and then quarterly until 96 weeks. Descriptive statistics and a mixed logistic model for longitudinal data evaluated the factors associated with high adherence. One thousand sixteen AMSM and ATGW accessed the PrEP1519 clinics. Of those, 998 (98.2%) underwent clinical triage. Forty one were diagnosed with human immunodeficiency viruses (HIV) at baseline (4.0%) and 79 (7.9%) were not eligible for PrEP. Of the 878, 795 (90.5%) enrolled in PrEP, 82 (10.3%) were lost to follow-up, and 713 were included. There was no significant decrease in creatinine clearance; only two participants had grade-III aspartate aminotransferase elevation. Incident HIV infection occurred in eight participants (incidence rate [IR] = 1.64 per 100 person-years [PY]): two in 15–17 years (IR = 2.24 per 100 PY) and six in 18–20 years (IR = 1.51 per 100 PY). PrEP adherence was higher among those with more years of schooling, those reporting no difficulties in PrEP use due to side effects, and who had low HIV risk perception in the past three months. PrEP for AMSM and ATGW was safe and feasible in real-world settings. However, a higher IR among young adolescents and a higher adherence among less vulnerable people indicate the need for greater care, considering the specificities of this age group. [ABSTRACT FROM AUTHOR]

This study analyzed the sociodemographic and behavioral characteristics of adolescent men who have sex with men (aMSM) and transgender women (aTGW) initiating oral pre-exposure prophylaxis (PrEP) in human immunodeficiency virus (HIV) prevention clinics. PrEP1519 is a prospective, multicenter, open-label PrEP demonstration cohort study of aMSM and aTGW aged 15–19 years living in three large Brazilian capital cities. For this analysis, we included adolescents who enrolled in PrEP1519 from February 2019 to August 2021. Adolescents who visited PrEP clinics were classified into four groups based on PrEP eligibility and on their decision to use PrEP: (1) ineligible for same-day PrEP initiation; (2) eligible for same-day PrEP initiation, initiated PrEP at first visit; (3) eligible for PrEP initiation, initiated PrEP after the first visit; and (4) eligible for same-day PrEP initiation but declined. The groups that were eligible for same-day PrEP initiation were compared using the Chi-square and Fisher's exact tests. Of the 1,254 adolescents enrolled in the PrEP1519 study, 61 (4.9%) were considered ineligible for same-day PrEP initiation. Of the 1,193 eligible for same-day PrEP initiation, 1,113 (93.3%) initiated PrEP [1,054 initiated PrEP in the first visit (88.3%) and 59 in subsequent visits (4.9%)] and 80 (6.7%) did not. Despite 90% of the PrEP decliners reporting a low risk of HIV infection, most reported condomless anal sex in the past six months (70%). Same-day PrEP initiation among aMSM and aTGW was high, highlighting that this strategy was important to promote PrEP initiation among adolescents with increased vulnerability to HIV in Brazil. [ABSTRACT FROM AUTHOR]

This study aimed at describing the prevalence of symptoms of depression among 15–19 year old adolescent men who have sex with men (aMSM) and transgender women (aTGW), who were recruited in an HIV pre-exposure prophylaxis cohort study in three Brazilian capital cities. The study also examined potential associations, including violence and discrimination, with severe symptoms of depression among aMSM. This is a cross-sectional study of baseline data among 730 aMSM and 56 aTGW recruited between February 2019 and February 2021. Sociodemographic and behavioral data were collected. The 20-item Center for Epidemiologic Studies Depression scale was used to screen for symptoms of depression. Scores of ≥22 points indicate the presence of severe symptoms associated with major depression. Logistic regression was used to assess independent associations among aMSM, adjusting for sociodemographic variables. Our findings indicate a high prevalence of symptoms of depression (overall prevalence = 58.5% and 69.6%; 21.2% and 25.0% for mild/moderate, and 37.3% and 44.6% for severe) among these aMSM and aTGW, respectively. Psychological violence (aOR = 1.74; 95% CI = 1.12–2.70), sexual violence (aOR = 1.79; 95% CI = 1.07–2.98), and discrimination due to sexual orientation (aOR = 1.71; 95% CI = 1.23–2.38) were independently associated with severe symptoms of depression in aMSM. The high prevalence of severe symptoms of depression and its association with psychological and sexual violence and discrimination creates cycles of vulnerability and carries important public health implications. Thus, our findings indicate public policies should consider assessing depression, psychological and sexual violence, as well as discrimination, especially in populations that will be targeted by interventions, such as the use of pre-exposure prophylaxis. [ABSTRACT FROM AUTHOR]

This study aimed to describe pre-exposure prophylaxis (PrEP) for HIV discontinuation in adolescent men who have sex with men (aMSM) and adolescent transgender women (aTGW) and to identify factors associated with discontinuation. The PrEP1519 study included a cohort of aMSM and aTGW aged 15–19 years old, and it was conducted in three large Brazilian capital cities. For this analysis, we included adolescents who initiated PrEP. PrEP discontinuation was defined as no possession of PrEP pills for >90 days. Kaplan-Meier curves were used to analyze the probabilities of discontinuation, and survival distributions stratified by covariates were compared using log-rank or Wilcoxon tests. Cox regression models were used to estimate the adjusted hazard ratio (aHR) with a 95% confidence interval (95% CI). We included 908 adolescents, 829 (91.30%) aMSM and 79 (8.70%) aTGW, most of whom were 18–19 years (80.29%). The incidence rate of discontinuation was 75.6 per 100 person-years. The probability of discontinuation was 52.61% in the first year. The multivariate analysis demonstrated that the aTGW (aHR = 1.63; 95% CI: 1.02–1.64) and adolescents with a medium (aHR = 1.29; 95% CI: 1.02–1.64) or low (aHR = 1.65; 95% CI: 1.29–2.12) perceived risk of HIV infection had an increased risk of discontinuation, whereas the adolescents with a partner living with HIV had a lower risk of discontinuation (aHR = 0.57; 95% CI: 0.35–0.91). Adolescents with a high risk for discontinuation may need additional support that emphasizes the value of PrEP as a tool for HIV prevention because PrEP discontinuation was associated with a disconnect between HIV risk perception and HIV prevention. [ABSTRACT FROM AUTHOR]

To explore legal and ethical challenges related to adolescents' participation in human immunodeficiency virus (HIV) research that may affect their best interests. We analyzed the ethical principles and legal aspects of the participation of 15–17-year-old men who have sex with men and transgender women in the pre-exposure prophylaxis (PrEP) 1519 study, a PrEP demonstration cohort study in three Brazilian cities. The analyses of ethics review committees' (ERCs) evaluations and court decisions followed ethical and human rights principles. An HIV vulnerability score was created, and descriptive statistics and multivariate logistic regression were performed using data from 347 participants. The ERCs evaluated the benefits and risks of research participation, all finding that the benefits outweighed the risks. ERCs deferred responsibility for decisions about waiving parental consent to the judiciary. State courts reached different decisions about waiving parental consent, reflecting variation in recognition of adolescents' evolving capacities and the adolescent as a subject of sexual rights and the primary agent capable of deciding on their health and best interests. The most vulnerable adolescent participants were found in sites where the blanket waiver was in place. Judicializing the ethical review process is detrimental to fulfilling the ethical principle of justice and vulnerable adolescents' access to health research. ERCs must be sufficiently independent and autonomous and have the capacity to respect, protect, and help fulfill the rights of participants while ensuring the generation of adequate evidence to inform public health practice. [ABSTRACT FROM AUTHOR]

This systematic review aims to estimate the prevalence of sarcopenia in people living with HIV (PLHIV) and to assess whether there is a difference between the muscle mass of PLHIV and people living without HIV. A systematic review of randomized controlled trials, cohort studies, cross-sectional and case-control studies was carried out. PLHIV over 18 years of age and that had their muscle mass evaluated by dual-energy X-ray absorptiometry were included. Overall, 4,376 studies were found, of which 118 had their full texts evaluated. A total of 5,532 people living with HIV and 2,986 people living without HIV were identified in 41 studies. The frequency of sarcopenia defined by low muscle mass (Baumgartner's operational definition) alone was 30.3% (95%CI 24.3%, 37.1%) and the frequency of sarcopenia defined by low muscle mass with low muscle strength (EWGSOP definition) was 4.5% (95%CI 1.3%, 13.9%), p -value = 0.0006. The standardized mean differences of muscle mass between PLHIV and controls was -0.211 units of standard deviation (95%CI -0.419, -0.003). In the meta-regression analysis muscle mass mean difference was associated with BMI, CD4, percentage of subjects on ART, and study design. PLHIV have a lower muscle mass when compared to people living without HIV. This difference appears to be attenuated by higher BMI, CD4 levels, and the percentage of subjects using ART. Furthermore, the frequencies of sarcopenia assessed by the operational definition of Baumgartner and the EWGSOP are not comparable and cannot be interchanged in PLHIV. [ABSTRACT FROM AUTHOR]

Abstract: Aims: To compare high-sensitivity C-reactive protein (hsCRP) in HIV-infected patients treated or not with antiretroviral (ARV) drugs and to correlate hsCRP levels with traditional cardiovascular risk factors and parameters of HIV infection. Methods: One hundred and seventy-one HIV-infected patients were included (129 ARV-treated and 42 ARV-naïve). Evaluations included anthropometric measurements, blood pressure, laboratory tests, ultrasonographic measurement of fat thickness and impedance analysis. Results: hsCRP levels were higher in ARV-treated compared to ARV-naïve patients (p <0.001). Seventy-two (56%) ARV-treated patients and 11 (26%) ARV-naïve patients had hsCRP concentrations >3mg/dl (high risk for cardiovascular complications) (OR 3.56; 95%CI: 1.55–8.29; p =0.001, χ 2 test). hsCRP levels correlated positively with waist measurement (p =0.004), waist-to-hip ratio (p <0.001), systolic (p =0.05) and diastolic (p =0.03) blood pressure, intra-abdominal fat thickness (p =0.02), triglycerides (p =0.001), total cholesterol (p =0.01), fasting glucose (p =0.01), and glucose (p <0.001) and insulin levels (p =0.02) measured 2h after load. No correlation was found between hsCRP levels and CD4 cell counts and HIV-viral load. Independent factors associated with hsCRP levels were therapy with current non-nucleoside reverse transcriptase inhibitors (NNRTI) (p =0.003), waist-to-hip ratio (p =0.006), fasting glucose (p =0.049) and glucose levels 2h after load (p =0.003) in multivariate analysis model 1 and current NNRTI therapy (p <0.001), protease inhibitor therapy (p =0.016) and cardiometabolic syndrome (p =0.022) in multivariate analysis model 2. Conclusion: hsCRP in HIV-infected patients is associated with traditional cardiovascular risk factors, principally in ARV-treated patients. hsCRP levels are not associated with CD4 cell counts and HIV-viral load and may constitute a marker for cardiovascular risk related to HIV infection and ARV therapy. [Copyright &y& Elsevier]

While the degree of COVID-19 vaccine accessibility and uptake varies at both national and global levels, increasing vaccination coverage raises questions regarding the standard of prevention that ought to apply to different settings where COVID-19 vaccine trials are hosted. A WHO Expert Group has developed guidance on the ethical implications of conducting placebo-controlled trials in the context of expanding global COVID-19 vaccine coverage. The guidance also considers alternative trial designs to placebo controlled trials in the context of prototype vaccines, modified vaccines, and next generation vaccines. [ABSTRACT FROM AUTHOR]

Detection of the SARS-CoV-2 virus in stools and sewage has recently been reported, raising the hypothesis of faecal-oral transmission. If confirmed, this could have far-reaching consequences for public health and for pandemic control strategies. In this paper, we argue that a comprehensive and more nuanced analysis is required to test this hypothesis, taking into consideration both environmental dynamics and the persistence of viral infectivity. First, we examine the evidence regarding the presence of the virus in stools and sewage. Then we discuss the current framework of disease transmission through water and excreta and how the transmission of a respiratory disease fits into it. Against this background, we propose a framework to test the faecal-oral hypothesis, unpacking the different environmental routes from faeces to the mouth of a susceptible person. This framework should not be seen as a confirmation of the hypothesis but rather as an expanded view of its complexities, which could help shaping an agenda for research into a number of unanswered questions. Finally, the paper briefly discusses practical implications, based on current knowledge, for containment of the pandemic. Unlabelled Image • Presence of SARS-CoV-2 in stools and wastewater has recently been reported. • A possible faecal-oral transmission of SARS-CoV-2 has been raised. • Different routes from faeces to the mouth of a susceptible person exist. • Water, surfaces and places with vectors can be transmission routes. • A framework is proposed to help shaping a research agenda. [ABSTRACT FROM AUTHOR]

Abstract: Background: Human immunodeficiency virus type 1 (HIV-1) subtype B predominates in Brazil, but in the southern region subtype C is the most frequent, followed by subtypes B, F1 and recombinant forms. In southern Brazil, these subtypes co-circulate in subjects with homogeneous demographic and clinical features, enabling a better understanding of the role of HIV-1 subtypes on the characteristics of infection. Objectives: To evaluate the prevalence of different HIV-1 subtypes in subjects with recent diagnosis for HIV infection in the extreme south of Brazil, and to study their association with demographic, behavioral, clinical and laboratorial characteristics. Study design: We have determined the genetic sequence of viral protease and reverse transcriptase (polymerase, connection and RNase H domains) isolated from studied subjects. Viral subtype was inferred by comparison with reference HIV sequences, and recombination was determined with Simplot analysis. The association of HIV-1 subtypes with studied characteristics was evaluated by chi-square, Fisher''s exact, Student''s t and Kruskal–Wallis tests. Results: Two hundred and forty-five HIV isolates were molecularly characterized, and the association with variables was studied for 233 (95.1%) patients. Of those, 46.8% followed AIDS defining criteria. HIV-1C was responsible for 56.3% of infections, and was associated with heterosexual transmission (p =0.001) and with higher CD4+ T-cell counts (p =0.02). Conclusions: The molecular epidemiology of HIV-1 in the southernmost Brazil is currently steady with predominance of HIV-1C. This is the first study showing a robust association of the infection by this subtype and heterosexual transmission in the state of Rio Grande do Sul, Brazil. [Copyright &y& Elsevier]

Abstract: Background: Major and accessory drug resistance mutations have been recently characterized in the C-terminal RT subdomains of HIV-1, connection and RNase H. However, their presence in treatment-naïve patients infected with HIV-1 non-B subtypes remains largely unknown. Objectives: To characterize the patterns of primary resistance at the C-terminal RT subdomains of HIV-1 infecting subjects in the southern region of Brazil, where HIV-1 subtypes B and C co-circulate. Study design: Plasma viral RNA was extracted from patients recently diagnosed for HIV infection (2005–2008). The protease and reverse transcriptase regions were PCR-amplified and sequenced. Infecting HIV subtypes were assigned by phylogenetic inference and drug resistance mutations were determined following the IAS consensus and recent reports on C-terminal RT mutations. Results: The major mutation to NNRTI T369I/V was found in 1.8% of patients, while A376S was present in another 8.3%. In the RNase H domain, the compensatory mutation D488E was more frequently observed in subtype C than in subtype B (p =0.038), while the inverse was observed for mutation Q547K (p <0.001). The calculated codon genetic barrier showed that 22% of subtype B isolates, but no subtype C, carried T360, requiring two transitions to change into the resistance mutation 360V. Conclusions: Major resistance-conferring mutations to NNRTI were detected in 10% of RT connection domain viral sequences from treatment-naïve subjects. We showed for the first time that the presence of specific polymorphisms can constrain the acquisition of definite resistance mutations in the connection and RNase H subdomains of HIV-1 RT. [Copyright &y& Elsevier]