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Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are potent and well tolerated. In Brazil, the first-generation NNRTI efavirenz is included in the majority of first-line antiretroviral treatment regimens. In this study, we evaluated the effectiveness of etravirine, a new second-generation NNRTI, among patients failing antiretroviral regimens containing first-generation NNRTIs. We assessed single resistance mutations to etravirine as well as complex resistance mutations profile and discuss the potential of introducing etravirine as salvage therapy.

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]

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Using baseline data from the PrEP1519 cohort, in this article we aimed to analyze: (i) the effectiveness of demand creation strategies (DCS) to enroll adolescent men who have sex with men (AMSM) and adolescent transgender women (ATGW) into an HIV combination prevention study in Brazil; (ii) the predictors of DCS for adolescents' enrollment; and (iii) the factors associated with DCS by comparing online and face-to-face strategies for enrollment. The DCS included peer recruitment (i.e., online and face-to-face) and referrals from health services and non-governmental organizations (NGOs). AMSM and ATGW who agreed to participate in the study could opt to enroll in either PrEP (PrEP arm) or to use other prevention methods (non-PrEP arm). Bivariate and multivariate analyses were conducted and logistic regression odds ratios were estimated. The DCS reached 4529 AMSM and ATGW, the majority of which were derived online (73.8%). Of this total, 935 (20.6%) enrolled to participate (76.6% in PrEP arm and 23.4% in non-PrEP arm). The effectiveness of enrolling adolescents into both arms was greater via direct referrals (235/382 and 84/382, respectively) and face-to-face peer recruitment (139/670 and 35/670, respectively) than online (328/3342). We found that a combination under DCS was required for successful enrollment in PrEP, with online strategies majorly tending to enroll adolescents of a higher socioeconomic status. Our findings reinforce the need for DCS that actively reaches out to all adolescents at the greatest risk for HIV infection, irrespective of their socioeconomic status. [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: This study aims at estimating the prevalence of Leishmania infection among HIV-infected patients through the use of non-invasive tests. The study was conducted in three Infectious Diseases Services in two large Brazilian cities, both endemic areas for visceral leishmaniasis. Three hundred and eighty-one asymptomatic patients were enrolled whose ages ranged from 19 to 58 years old; 63.5% were men; mean TCD4+ was 380 cells/μl; and mean viral load was 153800 copies/ml. All individuals were tested for Leishmania infection through: ELISA using crude Leishmania infantum (ELISA), ELISA using the recombinant K39 antigen (rK39), indirect fluorescent antibody test (IFAT) and PCR targeted to kDNA region. The tests’ positivity were: 10.8% (ELISA), 3.9% (IFAT), 0.8% (rK39), 6.3% PCR and 20.2% (overall, at least one positive test), with no statistical correlation between positivity and clinical and laboratorial variables. Concordance among tests was low (Kappa <0.20). Prevalence of Leishmania asymptomatic infection was high in this population, reinforcing the need for attention in the evaluation of HIV patients from endemic areas. New efforts are needed to develop more specific and sensitive tests to diagnose Leishmania asymptomatic infection. Highly active antiretroviral therapy (HAART) seems to have a protective role against disease progression in co-infected individuals. [Copyright &y& Elsevier]

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]

Aims: To compare the intra-abdominal fat thickness measured by ultrasound between HIV-infected patients treated or not with antiretroviral drugs and to correlate these visceral adiposity measurements to other parameters of cardiovascular risks. Methods: In a transversal observational study, 160 HIV-infected patients were recruited and divided in two groups, i.e., 123 antiretroviral (ARV)-treated and 37 ARV-naïve patients. These patients were submitted to anthropometric determinations, laboratorial analysis, ultrasonographic measurements of subcutaneous and intra- abdominal fat thickness and to tetrapolar bioelectrical impedance analysis in order to measure the body composition. Results: In the patients treated with highly active antiretroviral therapy (HAART) the intra-abdominal fat pad was significantly thicker than that of the untreated group (69 ± 21 mm, n = 123 vs. 60 ± 18 mm, n = 37; p = 0.03 Student’s t test). The intra-abdominal fat thickness correlated significantly with plasma triglyceride, total cholesterol, fasting glucose, glucose measurements 2 h after dextrose load, fasting insulin, HOMA-IR index, systolic and diastolic blood pressures, weight, BMI, WHR and caliper-measured total fat percentage. Conclusion: The results showed that antiretroviral therapy is associated with increased ultrasonographic measurements of visceral adiposity. Our data demonstrated a strong correlation between intra-abdominal fat thickness and independent risk factors of cardiovascular disease: atherogenic lipid profile and insulin resistance. Copyright © 2007 S. Karger AG, Basel [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]