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BACKGROUND: Host genetic factors play a major role with respect to susceptibility to infections. Many polymorphisms of the Toll-like receptors (TLRs), members of the innate immune response, are directly associated with the clinical outcomes following infection. The 2848 G/A variant (rs352140) of the TLR9 gene is associated with increased TLR9 expression. However, the impact of the genotypes of this SNP on HIV+, HCV+, and HCV+/HIV+ individuals is still debated. MATERIALS AND METHODS: This study investigated the 2848 G/A polymorphism in HCV infection, HIV infection, and HCV/HIV co-infection in a large sample of Brazilians (n = 1,182). Groups were initially compared without considering stratification by ethnicity and subsequently stratifying individuals between whites and non-whites. RESULTS: Considering non-white individuals, a significant difference between the HIV+/HCV+ group and controls was observed with the GG genotype serving as a protective factor (p = 0.023). Additionally, significant allelic differences were observed between the HCV+ group and controls (p = 0.042); between the HIV+/HCV+ group and controls (p = 0.011); and between the HIV+/HCV+ group and HIV+ individuals (p = 0.047). However, all significant results were lost following adjustment for multiple comparisons (p > 0.05). CONCLUSION: Although our initial results indicated a potential influence of the rs352140 genotype on host altered susceptibility to viral infections, following correction for multiple comparisions the standard (p

Chronic liver disease is an important cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) and is frequently related to non-alcoholic fatty liver disease (NAFLD). The objective is to estimate the prevalence and risk factors of hepatic steatosis among consecutive patients with stable HIV infection on antiretroviral therapy (ART). Also, the use of transient elastography (TE) as a mean to identify a subgroup at risk for non-alcoholic steatohepatitis (NASH) and/or liver fibrosis. HIV infected patients were enrolled between August2016 and February2017. Inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria: pregnancy; alcohol intake ≥20 g/day and co-infection B or C viruses. Patients underwent ultrasound (US) to diagnose liver steatosis. Significant fibrosis (≥F2) was estimated if at least one of the following were present: APRI > 1.0, FIB4 > 3 and/or liver stiffness ≥7.1kPa. Subjects with TE ≥ 7.1kPa were proposed a liver biopsy and NAFLD Scoring System (NAS) ≥ 3 was considered as diagnosis of NASH. A total of 98 patients were included. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male gender, BMI, ALT and total bilirubin levels. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients had a TE result ≥7.1kPa. NASH was found in 5 (83.3%). Among HIV infected patients undergoing ART, almost one third have NAFLD. Neither TE, APRI or FIB4 were able to act as surrogates for significant liver fibrosis. Nevertheless, TE ≥ 7.1kPa was able to accurately select a subgroup of patients at risk for NASH.

Summary Background Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19. Methods In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov , NCT04421027 . Findings Between June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of −2·7 percentage points (95% CI −7·3 to 1·9). The 28-day all-cause mortality was 8% (n=62) for baricitinib and 13% (n=100) for placebo (hazard ratio [HR] 0·57 [95% CI 0·41–0·78]; nominal p=0·0018), a 38·2% relative reduction in mortality; one additional death was prevented per 20 baricitinib-treated participants. The 60-day all-cause mortality was 10% (n=79) for baricitinib and 15% (n=116) for placebo (HR 0·62 [95% CI 0·47–0·83]; p=0·0050). The frequencies of serious adverse events (110 [15%] of 750 in the baricitinib group vs 135 [18%] of 752 in the placebo group), serious infections (64 [9%] vs 74 [10%]), and venous thromboembolic events (20 [3%] vs 19 [3%]) were similar between the two groups. Interpretation Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19. Funding Eli Lilly and Company. Translations For the French, Japanese, Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. \ud \ud \ud METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. \ud \ud \ud FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. \ud \ud \ud INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. \ud \ud \ud FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

HIV-infected individuals on chronic use of highly active antiretroviral therapy (HAART) are more likely to develop adipose tissue and metabolic disorders, such as lipodystrophy (LD) and metabolic syndrome (MetS). The development of these phenotypes is known to be multifactorial. Thus, variants in genes implicated in adipogenesis and lipid metabolism may increase susceptibility to LD and MetS. Sirtuin 1 (SIRT1) may influence the outcome of these disturbances due to its role in the regulation of transcription factors involved in energy regulation. Therefore, we genotyped four polymorphisms located in SIRT1 (rs2273773 T>C, rs12413112 G>A, rs7895833 A>G, rs12049646 T>C) in 832 HIV-infected patients receiving HAART by real-time polymerase chain reaction. The prevalence of LD was 55.8% and MetS was 35.3%. Lipoatrophy was the most prevalent subtype in all samples (38.0%) and showed significant difference between white and non-white individuals (P = 0.002). None of the genetic variants investigated in SIRT1 was associated with LD and MetS. White individuals and those in longer time of HAART use were more likely to develop LD. We concluded that these SIRT1 polymorphisms are not predictive factors to the development of lipodystrophy and metabolic syndrome in HIV-infected individuals from Brazil.

Background: Development of drug-resistance mutations is the main cause of failure in antiretroviral therapy. In Brazil, there is scarce information on resistance pattern for patients failing antiretroviral therapy. Objectives: To define the HIV mutational profile associated with drug resistance in Brazilian patients from 5 large cities, after first, second or further failures to antiretroviral therapy. Methods: We reviewed genotyping results of 1520 patients failing therapy in five Brazilian cities. Frequency of mutations, mean number of active drugs, viral susceptibility to each antiretrovirals drug, and regional differences were assessed. Results: Mean time of antiretrovirals use was 22.7 ± 41.1 months. Mean pre-genotyping viral load was 4.2 ± 0.8 log (2.1 ± 2.0 after switching antiretrovirals). Mean number of remaining active drugs was 9.4, 9.0, and 7.9 after 1st, 2nd, and 3rd failure, respectively. We detected regional variations in drug susceptibility: while BA and RS showed the highest (∼40%) resistance level to ATV/r, FPV/r and LPV/r, in the remaining cities it was around half of this rate. We detected 90% efavirenz/nevirapine resistance in SP, only 45% in RS, and levels between 25% and 30% in the other cities. Regarding NRTI, we found a similar pattern, with RJ presenting the highest, and CE the lowest susceptibility rates for all NRTI. Zidovudine resistance was detected in only 3% of patients in RJ, against 45–65% in the other cities. RJ and RS showed 3% resistance to tenofovir, while in CE it reached 55%. DRV/r (89–97%) and etravirine (61–85%) were the most active drugs, but again, with a wide variation across cities. Conclusions: The resistance mutational profile of Brazilian patients failing antiretroviral therapy is quite variable, depending on the city where patients were tested. This variation likely reflects distinctive choice of antiretrovirals drugs to initiate therapy, adherence to specific drugs, or circulating HIV-1 strains. Overall, etravirine and DRV/r remain as the most active drugs. Keywords: HIV, Resistance, Brazil, Mutations

Introdução: A terapia antirretroviral combinada (TARV) foi introduzida no Brasil em 1996, como parte da política nacional de acesso gratuito aos serviços de saúde e medicamentos. Infelizmente, o seu uso contínuo tem sido associado com mudanças na distribuição da gordura corporal e com alterações metabólicas que podem aumentar a morbidade e mortalidade nesta população. O treinamento físico tem sido estudado como uma estratégia eficaz de intervenção não farmacológica para melhorar os parâmetros de aptidão física relacionados à saúde e para minimizar os efeitos indesejáveis da infecção pelo HIV e/ou o uso prolongado da TARV, no entanto, há poucos estudos sobre o treinamento físico, síndrome lipodistrófica e cardiologia. Objetivo: Avaliar o risco de doença isquêmica cardíaca em sujeitos HIV/AIDS em uso de TARV praticantes de treinamento concorrente com séries simples. Métodos: Quatorze sujeitos foram avaliados através da circunferência abdominal, pressão arterial sistólica (PAS) e diastólica (PAD), colesterol total (CT), HDL, LDL, triglicerídeos (TG) e glicemia. Para a estimativa do risco coronariano em 10 anos utilizou-se o Escore de Framingham. Resultados: A maioria dos sujeitos situou-se dentro dos valores de referência para as variáveis analisadas, exceto para os valores de LDL e TG. Treze sujeitos (92,7%) ficaram abaixo dos 10% de risco coronariano em 10 anos, e apenas um (7,3%) estava em risco moderado. Houve correlação significativa entre o tempo de treinamento e a PAS. Conclusão: Sugere-se a realização de ensaios clínicos randomizados para avaliar os mesmos desfechos deste estudo. Introduction: Highly active antiretroviral therapy (HAART) was introduced to Brazil in 1996, as part of the national policy of free access to health services and drugs. Unfortunately, its continued use has been associated with changes in the redistribution of body fat, and metabolic changes which can increase morbidity and mortality in this population. Physical training has been studied as an effective strategy of non-pharmacological intervention to improve physical fitness parameters related to health and to minimize the undesirable effects of HIV infection and/or prolonged use of HAART. However, there are few studies on physical training, lipodystrophy syndrome and cardiology. Objective: To assess the risk of ischemic heart disease in HIV/AIDS subjects on HAART and in concurrent training with single sets. Methods: Fourteen subjects were assessed by waist circumference, systolic (SBP) and diastolic (DBP) blood pressure, lipid profile, total cholesterol (TC), HDL, LDL, triglycerides (TG) and glucose. The Framingham score was used to estimate the 10-year risk for coronary heart disease. Results: Except for LDL and TG values, most subjects were within the reference limits for the analyzed variables. Thirteen subjects (92.7%) were below the range of 10% for the 10-year risk for coronary heart disease, while only one subject (7.3%) showed a moderate risk. There was a significant correlation between training time and the SBP variable. Conclusion: We suggest conducting randomized trials to assess the same outcomes of this study. Introducción: La terapia antirretroviral de gran actividad (HAART) se introdujo en Brasil en 1996, como parte de la política nacional de acceso gratuito a los servicios de salud y medicamentos. Desafortunadamente, su uso continuado se ha asociado con cambios en la distribución de la grasa corporal y los cambios metabólicos que pueden aumentar la morbilidad y la mortalidad en esta población. El entrenamiento físico se ha estudiado como una estrategia de intervención no farmacológica eficaz para mejorar los parámetros de la condición física relacionados con la salud y reducir al mínimo los efectos adversos de la infección por VIH y/o el uso prolongado de la terapia HAART, sin embargo, existen pocos estudios sobre entrenamiento físico, el síndrome de lipodistrofia y cardiología. Objetivo: Evaluar el riesgo de cardiopatía isquémica en pacientes con VIH/SIDA que reciben HAART que practican entrenamiento concurrente con series simples. Métodos: Catorce sujetos se evaluaron utilizando la circunferencia de cintura, presión arterial sistólica (PAS) y diastólica (PAD), colesterol total (CT), HDL, LDL, triglicéridos (TG) y la glucosa. Para estimar el riesgo coronario en 10 años se utilizó el score de Framingham. Resultados: La mayoría de los sujetos estaban dentro de los límites de referencia de las variables analizadas, a excepción de LDL y TG. Trece sujetos (92,7%) estaban por debajo del riesgo coronario del 10% en 10 años, y sólo uno (7,3%) tenía riesgo moderado. Hubo una correlación significativa entre la duración del entrenamiento y la PAS. Conclusión: Se sugiere llevar a cabo ensayos clínicos aleatorios para evaluar los mismos resultados de este estudio

O objetivo deste estudo é avaliar o nível de conhecimento sobre HIV/aids nos indivíduos de meia idade, participantes de grupos de convivência do Vale do Sinos (RS). O estudo caracterizou-se como transversal, obtendo-se uma amostra de 168 indivíduos, sendo 9,5% homens e 90,5% mulheres, na faixa etária entre 40 e 59 anos. Utilizou-se como instrumento um questionário composto pelos domínios "conceito", "transmissão", "vulnerabilidade", "prevenção" e "tratamento". O ensino fundamental caracterizou 61,3% da escolaridade dos participantes e a renda mensal situou-se entre um e três salários mínimos para 45,2%. No domínio "conceito", 65,2% desconheciam a fase assintomática da infecção e 34,5% apontaram o mosquito como transmissor da aids, no domínio "transmissão". Nos domínios "prevenção" e "vulnerabilidade", 19,5% desconheciam a existência do preservativo feminino e 29,2% acreditaram que a doença é característica de grupos específicos. Quanto ao "tratamento", 12,5% ignoraram a sua existência. De acordo com os achados, os indivíduos da meia idade participantes de grupos de convivência do Vale do Sinos tinham conceitos errôneos sobre HIV/aids que poderiam aumentar o risco à infecção. Sendo assim, é necessário proporcionar programas de saúde pública direcionados para esta população para prevenir ou diminuir o risco de transmissão do HIV.The objective of this article is to assess the knowledge about HIV/aids in middle aged acquaintance group participants from the Vale do Sinos, Rio Grande do Sul State, Brazil. A prospective cross-sectional study with 168 individuals (9.5% male and 90.5% female) between 40 and 59 years of age was performed. A questionnaire comprising questions about the concept, transmission, vulnerability, prevention, and treatment domains on HIV issues was constructed. It was observed that 61.3% of the sample had finished elementary education and 45.2% had a monthly income ranging from 1 to 3 minimum wages. In the conceptual domain, 65.2% did not know that HIV infection has an asymptomatic phase and 34.5% believed HIV could be transmitted by a mosquito bite. In prevention and vulnerability domains, 19.5% had no knowledge about female condoms and 29.2% believed that the disease was confined to specific groups. Regarding to antiretroviral treatment, 12.5% had no idea about its existence. According to findings, middle aged participants from acquaintance groups in Vale do Sinos had misconceptions about HIV/aids which might enhance the risk of infection. Therefore it is necessary to provide public health programs directed to this population group in order to prevent or decrease the risk of HIV transmission.

O uso da terapia anti-retroviral combinada (TARV) aumentou a expectativa de vida dos portadores do vírus da imunodeficiência humana (HIV) e, como conseqüência, torna-se constante o estudo do processo fisiopatológico da infecção e das estratégias de intervenção que possam melhorar a qualidade de vida destes indivíduos. O treinamento concorrente, definido como a associação dos componentes aeróbios e força na mesma sessão de exercícios pode ser inserido neste contexto. O objetivo deste artigo é revisar os aspectos centrais da infecção pelo HIV e as evidências existentes sobre o treinamento concorrente com séries múltiplas e simples nos parâmetros imunológico, virológico, cardiorrespiratório e neuromuscular de pessoas infectadas pelo HIV. O método utilizado foi uma revisão sistemática, com artigos publicados entre 2000-2007, nas bases de dados scielo e pubmed e também em dissertações e teses da biblioteca digital da educação física, esporte e saúde. As evidências científicas encontradas nos 8 estudos analisados indicam que o treinamento concorrente, tanto com séries múltiplas quanto séries simples, melhora os parâmetros cardiorrespiratório e neuromuscular; no entanto, os resultados dos parâmetros imunológico e virológico ainda não estão completamente esclarecidos, principalmente sobre os protocolos com séries simples. Considerando o número restrito de trabalhos apresentados, sugere-se o desenvolvimento de estudos com treinamento concorrente em vários desfechos clínicos para pessoas infectadas pelo HIV.The highly active antiretroviral therapy (HAART) increased life expectancy in individuals infected with the human immunodeficiency virus (HIV). Alternative strategies have been used in order to improve their quality of life and minimize the HAART effect; among these we can name physical exercise. Concurrent training, the combination of aerobic and strength training in the same exercise session, is used to improve aerobic and strength capacities with shorter time of training and stands out within the used methods. It is crucial to understand this syndrome's characteristics for the best application of physical exercise in the HIV infected patients. Therefore, the aim of this study is to review the main HIV infection characteristics and the evidence available on concurrent training with single and multiple sets in immunological, virological, cardiorespiratory and neuromuscular parameters in subjects living with HIV/AIDS. A systematic review of papers published from 2000-2007 in the Scielo and Pubmed database, as well as theses and dissertations on Physical Education, Sports and Health fields from the digital library totalizing 8 studies, was performed. Evidence from these 8 investigated studies showed that concurrent training, both with single and multiple sets, improves cardiorespiratory and neuromuscular parameters. However, the results in the immunological and virological parameters are not completely understood, especially on protocols with single sets.

O objetivo deste estudo é avaliar o conhecimento sobre HIV/aids dos participantes de grupos de convivência do Vale do Sinos, Rio Grande do Sul. O estudo caracterizou-se como transversal, obtendo-se uma amostra de 510 pessoas, sendo 17,5% homens e 82,5% mulheres, na faixa etária entre 60-90 anos. Utilizou-se o questionário sobre HIV para terceira idade, que abrange características gerais dos participantes e questões relativas à aids, organizadas nos domínios "conceito", "transmissão", "prevenção", "vulnerabilidade" e "tratamento". Quase metade (48,4%) dos participantes relatou ter cursado de quatro a sete anos de estudo e a renda mensal de 52,2% foi de um a três salários mínimos. Nos domínios "conceito" e "transmissão", 49,4% desconheciam a fase assintomática da infecção pelo HIV e 41,4% acreditavam que a aids poderia ser transmitida pelo mosquito. No âmbito dos domínios "prevenção" e "vulnerabilidade", 25,5% não sabiam da existência da camisinha feminina e 36,9% consideravam a aids uma síndrome somente de homens que fazem sexo com homens, profissionais do sexo e usuários de drogas. Quanto ao "tratamento", 12,2% ignoravam a sua existência. Constataram-se lacunas no conhecimento sobre HIV/aids na amostra avaliada, demonstrando a necessidade de programas de saúde pública que visem à elucidação das principais dúvidas.The objective of this study was to assess the knowledge about HIV/AIDS in participants of companionship groups in the Vale do Sinos, Rio Grande do Sul, Brazil. It was a prospective cross-sectional study in a sample of 510 individuals, 17% males and 82.5% females aged between 60 and 90 years. We used the Questionnaire on HIV for the Old Aged, which comprises the general characteristics of the participants and questions concerning HIV/AIDS, organized into the elements 'concept', 'transmission', 'prevention', 'vulnerability', and 'treatment'. Nearly half of the participants (48.4 %) reported having studied 4 to 7 years and the monthly income of 52.2% was of 1 to 3 minimum wages. In the dimensions concept and transmission, 49.4% had no idea about the asymptomatic phase of the infection, and 41.4% believed HIV could be transmitted by a mosquito bite. With regard to prevention and vulnerability, 25.5% did not know about the female condom and 36.9% considered AIDS a disease confined to men who have sex with men, sex workers, and injection-drug users. Regarding antiretroviral treatment, 12.2% ignored its existence. Elderly people in companionship groups have important misconceptions about HIV/AIDS, which can increase their risk of infection. There is a need for public health programs directed to this population in order to prevent or decrease the risk of HIV transmission.

Objective: This study aimed to investigate the role of Human Leukocyte Antigen (HLA)-G in the susceptibility to HIV-1 infection through the analysis of the HLA-G 30 untranslated region (UTR) polymorphisms 14 bp insertion/deletion (rs66554220) and +3142C>G (rs1063320). Design: We analyzed 582 HIV-1 infected patients and 626 uninfected individuals from Brazil and Italy in a case-control study. Methods: HLA-G polymorphisms were genotyped using PCR, PCR-RFLP assays or direct sequencing. All analyses were stratified by ethnicity. Genotypic, allelic and diplotypic frequencies were compared between HIV-1 infected subjects and controls using Chi-square or Fischer exact tests. Also, haplotypic frequencies were estimated using MLocus software. Results: African-derived HIV-infected individuals presented a higher frequency of the 14 bp insertion allele as compared to non-infected individuals (0.468 versus 0.373, respectively; pBonf = 0.010). A higher frequency of the 14 bp insertion +3142G (insG) haplotype (0.456 versus 0.346, p < 0.001) and the insG/ insG diplotype (OR = 1.88, 95%CI = 1.08–3.23, p = 0.021) was observed among African-derived patients as compared to uninfected controls. Also, we observed a higher frequency of the ins/ins genotype among African-derived HIV patients co-infected with HCV (OR = 2.78, 95%CI = 1.20–6.49, p = 0.008). Conclusions: Our data point out to an increased frequency of alleles and genotypes associated with low HLA-G expression among African-derived patients, suggesting a potential role for HLA-G in the susceptibility to HIV-1 infection and HCV co-infection in those individuals.

A infecção pelo vírus da imunodeficiência humana (HIV) é acompanhada por alterações estruturais e funcionais relacionadas ao sistema imunológico. Além disso, o aumento do estresse oxidativo (EO) nos portadores do HIV, caracterizado por diminuição nos níveis de glutationa (GSH), aumentos na glutationa oxidada (GSSG), na razão GSSG/GSH e lipoperoxidação, bem como redução da atividade de enzimas antioxidantes - catalase, superóxido dismutase (SOD) e glutationa peroxidase (GPx) - é uma conseqüência da evolução dos pacientes infectados com HIV. As células do sistema imunológico necessitam de altas concentrações de antioxidantes para manter o balanço redox e preservar a sua integridade e função. Quando ocorre a depleção dos antioxidantes, há diminuição da resposta imunológica e aumento na replicação do HIV. O uso da terapia anti-retroviral combinada (TARV) melhorou significativamente a evolução clínica dos pacientes, porém, mesmo assim, alguns continuam apresentando EO aumentado e outros efeitos da TARV, como alterações no metabolismo lipídico e muscular. O treinamento físico é utilizado como intervenção não farmacológica nos pacientes infectados pelo HIV para proporcionar melhoria nos parâmetros antropométricos, aeróbios, musculares e psicológicos, porém, há carência de estudos sobre a sua utilização em relação ao estresse oxidativo. Nesta revisão, foram analisados os tópicos referentes ao estresse oxidativo nos pacientes HIV positivos e os possíveis benefícios do exercício físico na capacidade antioxidante. O treinamento físico é uma estratégia auxiliar para os pacientes, com ou sem uso da TARV, uma vez que melhora os aspectos cardiorrespiratórios, musculares, antropométricos e psicológicos sem induzir a imunossupressão. Referindo-se ao estresse oxidativo, infere-se, a partir dos dados em indivíduos HIV negativos, que o treinamento físico pode gerar adaptações que minimizam os efeitos deletérios provocados pelo EO através de melhorias nos níveis das defesas antioxidantes enzimáticas e não enzimáticas.Human immunodeficiency virus (HIV) infection is characterized by functional and structural changes related to the immunological system. Moreover, increase in oxidative stress (OS) in HIV patients, characterized by a reduction in the glutathione (GSH) levels, increases in glutathione disulfide (GSSG), in the ratio GSSG/GSH and in lipid peroxidation, as well as a reduction in antioxidant enzymes - catalase, superoxid dismutase (SOD) and gluthatione peroxidase (GPx) - is a consequence of the evolution in HIV-infected patients. Higher levels of antioxidant activity are necessary to maintain the immunological system cells redox balance and preserve their function. In an antioxidant depleted state, there is a reduction in the immunological response and an increase in HIV replication. The use of highly active antiretroviral therapy (HAART) has improved the clinical evolution of these patients. However, some patients remain showing higher OS and other effects of HAART, such as changes in lipidic and muscle metabolism. Exercise training has been used as a non pharmacological treatment in HIV-infected patients to promote improvements in anthropometrics, aerobic, muscle and psychological outcomes; however, there are insufficient data about the effects of exercise training in OS. This review analyzes the topics related to the oxidative stress in HIV-infected patients and the possible benefits of the physical exercise in the antioxidant capacity. Physical training is a complementary procedure for the patients, with or without use of the HAART, since it improves the cardiorespiratory, muscle, anthropometrics and psychological performance without inducing immunodepression. In relation to oxidative stress, it is inferred, from the data obtained in non-HIV individuals, that the physical training could promote adaptations that minimize the deleterious effect induced by OS through improvements in the activity of the enzymatic and non-enzymatic antioxidant defenses.

The prognosis of human immunodeficiency virus (HIV)-infected individuals has dramatically improved worldwide since the introduction of highly antiretroviral therapy. Nevertheless, along with the decrease in mortality, several body modifications not initially related to HIV infection have been reported. Disorders in lipid and glucose metabolism, accompanied by body shape abnormalities and alterations in fat distribution, began to be described. A syndrome, named “HIV-associated lipodystrophy syndrome”, was coined to classify these clinical spectrum aspects. This syndrome involves not only metabolic alterations but also fat redistribution, with lipoatrophy due to subcutaneous fat loss (predominantly in the face and lower limbs) and lipohypertrophy related to central fat gain. These changes in body shape are very important to be recognized, as they are associated with worse morbidity and mortality. Self-esteem difficulties related to body alterations might lead to treatment failures due to medication adherence problems. Moreover, these alterations have been associated with an increased risk of cardiovascular events. Therefore, it is extremely important to identify this syndrome early in order to provide an even better quality of life for this population, as the clinical approach is not easy. Treatment change, medications to treat dyslipidemia, and surgical intervention are instruments to be used to try to correct these abnormalities. The aim of this study is to review clinical presentation, diagnosis, and management of body shape and metabolic complications of HIV infection from a Brazilian perspective, a medium income country with a large number of patients on antiretroviral therapy.

Objective: To evaluate the factors associated with plasma concentrations of atazanavir (ATV) in a cohort of well-controlled HIV infected subjects (undetectable viremia). Design: Cross-sectional study where 69 subjects were consecutively enrolled between April and November, 2011. Methods: Patients had to be on atazanavir for at least six months, undetectable viral load for a period equal to or longer than 12 months, T CD4+ lymphocyte count higher than 200 cells/mm3, and aged between 18 years and 70 years old. Exclusion criteria were pregnancy, any neurologic disease, active opportunistic disease, hepatitis or cancer. Atazanavir plasma levels were measured by ultra-performance liquid chromatography. Results and discussion: Overall, 54 patients (mean age of 47 years and 50% women) were included in the analysis. Those without ritonavir (unboosted atazanavir) had statistically lower plasma concentrations than those with ritonavir boosted atazanavir (p = 0.001) and total and indirect bilirubin were statistically associated with plasma concentration of atazanavir (r = 0.32 and r = 0.33 respectively; p

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, andLDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%).APOE(rs429358 and rs7412) genotypes andAPOA5−1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). TheAPOA5−1131T>C (rs662799) andSCAP2386A>G (rs12487736) polymorphisms were significantly associated with high-density-lipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both theAPOBSPIns/Del(rs17240441) andAPOB XbaI(rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.

Background Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART. Method Naïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART. Results 3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/μL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12. Conclusion In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART.

Objective: To investigate genetic single nucleotide polymorphisms (SNPs) in estrogen receptor-a (ERa) (ESR1, rs2234693, rs1801132, rs7757956 and rs2813544) and ERb (ESR2, rs3020450, rs7154455 and rs4986938) genes and relate them to the adverse effects lipodystrophy, dyslipidemia and metabolic syndrome as well as to differences in their prevalence between sexes in HIV-infected individuals on HAART. Design: Cross-sectional study. Methods: Blood samples and anthropometric measurements were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas and Rio Grande in Brazil. The SNPs were genotyped by real-time PCR. Results: The lipodystrophy subtype frequencies in patients of different sexes showed statistically significant differences; the atrophic pattern was more prevalent in men, and the hypertrophic pattern was more prevalent in women. Furthermore, metabolic syndrome prevalence was higher in women than in men. The ESR1 rs2813544 G-allele was associated with higher measurements of several anthropometric variables in women: BMI, total subcutaneous fat and subcutaneous fat of limbs. Additionally, patients who were AA homozygous for ESR2 rs3020450 presented an increased risk for developing lipoatrophy (prevalence ratio 1.37, 95% confidence interval 1.09–1.73, P ¼ 0.007). Conclusion: Significant differences in lipodystrophy and metabolic syndrome prevalence were detected between sexes. Moreover, the ESR1 gene (rs2813544) presented significant sex-specific associations with anthropometric variables, and the ESR2 gene (rs3020450) was associated with an increased risk of developing lipoatrophy. Our results suggest that these genes are in part responsible for the sexual dimorphism in fat tissue redistribution and patterns of lipodystrophy.