Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection

ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

The role of IFN-γ production during retroviral infections: an important cytokine involved in chronic inflammation and pathogenesis

ABSTRACT Interferon-gamma (IFN-γ) plays a crucial role in viral infections by preventing viral replication and in the promotion of innate and adaptive immune responses. However, IFN-gamma can exert distinct effects in different persistent viral infections. The long-term overproduction of IFN-γ in retroviral infections, such as the human immunodeficiency virus (HIV), human T-lymphotropic virus type 1 (HTLV-1), and human endogenous retroviruses (HERVs), resulting in inflammation, may cause neuronal damage. This review is provocative about the role of IFN-γ during persistent retroviral infections and its relationship with the causation of some neurological disorders that are important for public health.

Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: infecção pelo vírus linfotrópico de células T humanas (HTLV) / Brazilian Protocol for Sexually Transmitted Infections 2020: human T cell lymphotropic virus (HTLV) infection / Protocolo Brasileño para Infecciones de Transmisión Sexual 2020: infección por virus linfotrópico de células T humanas (HTLV)

O artigo aborda a infecção pelo vírus linfotrópico de células T humanas (human T lymphotropic virus, HTLV), tema contemplado no Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil. A infecção pelo HTLV-1/2 é um problema de saúde pública mundial, sendo o Brasil o país a referir o maior número de indivíduos convivendo com o vírus. O HTLV-1 causa diversas manifestações clínicas, de natureza neoplásica, como a leucemia/linfoma de células T do adulto, e de natureza inflamatória, a exemplo da mielopatia associada ao HTLV-1 e outras alterações, como uveíte, artrite e dermatite infecciosa. Estas patologias apresentam elevada morbimortalidade e impactam negativamente a qualidade de vida dos indivíduos infectados. A presente revisão inclui informações relevantes para gestores e profissionais de saúde sobre os mecanismos de transmissão viral, diagnóstico, tratamento e acompanhamento de indivíduos vivendo com o HTLV-1/2 no Brasil.

This manuscript is related to the chapter about human T-cell lymphotropic virus (HTLV) that is part of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Health Ministry. HTLV-1/2 infection is a worldwide public health problem and Brazil has the largest number of individuals living with the virus. HTLV-1 causes a variety of clinical manifestations of a neoplastic nature, such as adult leukemia/T-cell lymphoma, and also of an inflammatory nature, such as HTLV-1-associated myelopathy, as well as other manifestations such as uveitis, arthritis and infective dermatitis. These pathologies have high morbidity and mortality and negatively impact the quality of life of infected individuals. This review includes relevant information for health service managers and workers regarding virus transmission modes, diagnosis, treatment and monitoring of individuals living with HTLV-1 and 2 in Brazil.

El artículo está relacionado con el capítulo sobre virus linfotrópico de células T humanas (human T lymphotropic virus, HTLV) que conforma el Protocolo Clínico y Directrices Terapéuticas para la Atención Integral a Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil. La infección por HTLV-1/2 es un problema de salud pública en el mundo y Brasil tiene el mayor número de personas que viven con el virus. El HTLV-1 causa varias manifestaciones clínicas, de naturaleza neoplásica (leucemia/linfoma de células T adultas), y de naturaleza inflamatoria, como la mielopatía asociada al HTLV-1 y otras manifestaciones como la uveítis, la artritis y la dermatitis infecciosa. Estas patologías tienen una alta morbilidad y mortalidad e impactan negativamente en la calidad de vida de las personas infectadas. Esta revisión incluye información relevante para gerentes y profesionales de la salud sobre los mecanismos de transmisión viral, diagnóstico, tratamiento y monitoreo de personas que viven con HTLV-1 y 2 en Brasil.

Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: infecção pelo vírus linfotrópico de células T humanas (HTLV) / Brazilian Protocol for Sexually Transmitted Infections 2020: human T cell lymphotropic virus (HTLV) infection / Protocolo Brasileño para Infecciones de Transmisión Sexual 2020: infección por virus linfotrópico de células T humanas (HTLV)

Resumo O artigo aborda a infecção pelo vírus linfotrópico de células T humanas (human T lymphotropic virus, HTLV), tema contemplado no Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis, publicado pelo Ministério da Saúde do Brasil. A infecção pelo HTLV-1/2 é um problema de saúde pública mundial, sendo o Brasil o país a referir o maior número de indivíduos convivendo com o vírus. O HTLV-1 causa diversas manifestações clínicas, de natureza neoplásica, como a leucemia/linfoma de células T do adulto, e de natureza inflamatória, a exemplo da mielopatia associada ao HTLV-1 e outras alterações, como uveíte, artrite e dermatite infecciosa. Estas patologias apresentam elevada morbimortalidade e impactam negativamente a qualidade de vida dos indivíduos infectados. A presente revisão inclui informações relevantes para gestores e profissionais de saúde sobre os mecanismos de transmissão viral, diagnóstico, tratamento e acompanhamento de indivíduos vivendo com o HTLV-1/2 no Brasil.

Abstract This manuscript is related to the chapter about human T-cell lymphotropic virus (HTLV) that is part of the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Health Ministry. HTLV-1/2 infection is a worldwide public health problem and Brazil has the largest number of individuals living with the virus. HTLV-1 causes a variety of clinical manifestations of a neoplastic nature, such as adult leukemia/T-cell lymphoma, and also of an inflammatory nature, such as HTLV-1-associated myelopathy, as well as other manifestations such as uveitis, arthritis and infective dermatitis. These pathologies have high morbidity and mortality and negatively impact the quality of life of infected individuals. This review includes relevant information for health service managers and workers regarding virus transmission modes, diagnosis, treatment and monitoring of individuals living with HTLV-1 and 2 in Brazil.

Resumen El artículo está relacionado con el capítulo sobre virus linfotrópico de células T humanas (human T lymphotropic virus, HTLV) que conforma el Protocolo Clínico y Directrices Terapéuticas para la Atención Integral a Personas con Infecciones de Transmisión Sexual, publicado por el Ministerio de Salud de Brasil. La infección por HTLV-1/2 es un problema de salud pública en el mundo y Brasil tiene el mayor número de personas que viven con el virus. El HTLV-1 causa varias manifestaciones clínicas, de naturaleza neoplásica (leucemia/linfoma de células T adultas), y de naturaleza inflamatoria, como la mielopatía asociada al HTLV-1 y otras manifestaciones como la uveítis, la artritis y la dermatitis infecciosa. Estas patologías tienen una alta morbilidad y mortalidad e impactan negativamente en la calidad de vida de las personas infectadas. Esta revisión incluye información relevante para gerentes y profesionales de la salud sobre los mecanismos de transmisión viral, diagnóstico, tratamiento y monitoreo de personas que viven con HTLV-1 y 2 en Brasil.

Prevalence of infection by human T Cell lymphotropic viruses (HTLV-1/2) in adult population in Vitoria-ES

ABSTRACT Introduction: Brazil has a high number of HTLV-1/2 infections which are unequally distributed in the country. Most prevalence studies have focused on specific populations, such as blood donors and pregnant women. Some areas, for example the state of Bahia, have robust information about HTLV-1/2 infection, however there is no information available about this infection in the general population of Vitoria, Espírito Santo, Brazil. Objective: To determine the prevalence of HTLV-1/2 infection in adults from the municipality of Vitoria, ES. Methods: A cross sectional study was performed from September 2010 to December 2011, in individuals of both sexes, aged 18 or older living in Vitoria-ES. Venous blood samples were collected and tested for anti-HTLV-1/2 antibodies by chemiluminescent immunoassay (CMIA). Individuals with CMIA reactive results were submitted to a new blood collection for retesting by CMIA, followed by PCR to confirm infection and discriminate the viral type. Results: From 1502 tested samples, eight were reactive in CMIA and all were confirmed by PCR. Therefore, the prevalence of HTLV-1/2 was 0.53% (8/1502, 95% CI: 0.2-1.0%). The infection rate was 0.7% in men (5/711, 95% CI: 0.17-1.51%), and 0.38% in women (3/791, 95% CI: 0 -0.81%). Conclusions: The prevalence of HTLV-1/2 infection was 0.53% (8/1502; 95% CI: 0.2 -0.9%). Confirmatory test using real-time PCR (qPCR) identified seven individuals positive for HTLV-1 and one for HTLV-2. Considering the risk of infected individuals to develop high morbidity and mortality diseases, it would be important to implement public health policies aimed at stopping transmission of these viruses in this municipality. 2021 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license

Efficacy of vitamin D supplementation among persons living with HIV/AIDS in São Paulo city, Brazil

ABSTRACT Hypovitaminosis D is now considered a pandemic, especially among more vulnerable populations and in HIV-infected subjects, with 80% presenting levels below 30 ng/mL. As there is no consensus on the more adequate dosage needed to correct such deficiency, the objective of this study was to evaluate 25 (OH) vitamin D supplementation in HIV-1 patients deficient of vitamin D. A total of 73 HIV-1-infected patients were included, drawn from a cohort of 435 patients; 37 patients were randomized to the active group, supplemented once a week with 50,000 UI vitamin D by mouth (group 1) and 36 to the placebo group (group 2). The study period ranged from June 2016 to September 2017. Variables involved in vitamin D metabolism and risk factors associated with hypovitaminosis were evaluated. The mean age was 45 years and 31.5 % were women. Vitamin D supplementation was effective in normalizing serum levels after six months in group 1 (mean 35 ng/mL compared to 21 ng/mL for the placebo group; p= 0.04). No patient reached blood levels considered toxic (>100 UI). Efavirenz use can negatively influence vitamin D levels and supplementation is necessary as a likely adjunct to improving CD4+ T cells, resulting in greater effectiveness of the treatment. A weekly oral dose of 50,000 IU of vitamin D was sufficient to normalize the vitamin deficiency, safely and with good adherence among persons living with HIV/AIDS in Brazil.

Brazilian protocol for sexually transmitted infections 2020: human T-cell lymphotropic virus (HTLV) infection

Abstract This article addresses the Human T-lymphotropic virus (HTLV). This subject comprises the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health. HTLV-1/2 infection is a public health problem globally, and Brazil has the largest number of individuals living with the virus. HTLV-1 causes several clinical manifestations of neoplasm (adult T-cell leukemia/lymphoma) and inflammatory nature, such as HTLV-1-associated myelopathy and other manifestations such as uveitis, arthritis, and infective dermatitis. These pathologies have high morbidity and mortality and negatively impact the quality of life of infected individuals. This review includes relevant information for health authorities professionals regarding viral transmission, diagnosis, treatment, and monitoring of individuals living with HTLV-1 and 2 in Brazil.

Association between changes in body fat distribution, biochemical profile, time of HIV diagnosis, and antiretroviral treatment in adults living with and without virus infection

SUMMARY OBJECTIVES Individuals living with HIV seem to be more prone to changes in the redistribution of body fat, characterized as lipodystrophy, which may occur in conjunction with metabolic diseases. In the present study, such impacts were assessed in adults with and without HIV and associated with the time of virus diagnosis and treatment with antiretroviral. METHODS A cross-sectional study with 123 adults, in which 87 had HIV and 36 without HIV, of both sexes, in outpatient follow-up at the Specialized Care Service (SAE) in Macaé-RJ. The following were made: 1) Alteration in body fat distribution, measured by anthropometric parameters and self-reported lipodystrophy; 2) Biochemical profile; 3) Association between HIV diagnosis time and antiretroviral treatment. RESULTS 54.47% (n = 67) males, 45.52% (n = 56) females, mean age 37 years. Of these 87 were people living with HIV, 29% (n = 25) had self-reported lipodystrophy, mean time of virus infection, and antiretroviral treatment (5.80 ± 4.56 and 5.14 ± 3.82 years), respectively. Patients with self-reported lipodystrophy had a greater change in body fat distribution between 3-6 years of HIV diagnosis and a negative cholesterol profile. The antiretroviral treatment time influenced total cholesterol and triglycerides, even for patients without self-reported lipodystrophy, with a further nine years under treatment. CONCLUSION In this study, the negative cholesterol profile was mainly related to antiretroviral treatment time, even for patients without self-reported lipodystrophy, and changes in body fat distribution, measured by anthropometry, was especially associated with time for HIV infection in those with lipodystrophy self-reported.

RESUMO OBJETIVOS Indivíduos vivendo com HIV parecem mais propensos às alterações na redistribuição da gordura corporal, caracterizada como lipodistrofia, podendo acontecer em conjunto com as metabólicas. No presente estudo avaliaram-se tais impactos em adultos com e sem HIV e se associou ao tempo de diagnóstico do vírus e tratamento com antirretroviral. MÉTODOS Estudo tipo transversal, com 123 adultos, no qual 87 tinham HIV e 36 sem HIV, de ambos os sexos, em seguimento ambulatorial no Serviço de Atendimento Especializado (SAE) em Macaé - RJ. Foram feitos: 1) Alteração na distribuição da gordura corporal, mensurados por parâmetros antropométricos e lipodistrofia autorreferida; 2) Perfil bioquímico; 3) Associação entre tempo diagnóstico do HIV e tratamento com antirretroviral. RESULTADOS Incluíram-se 54,47% (n=67) do sexo masculino, 45,52% (n=56) do feminino, com média de idade de 37 anos. Destes, 87 eram pessoas vivendo com HIV, 29% (n=25) possuíam lipodistrofia autorreferida; tempo médio de infecção pelo vírus e tratamento antirretroviral (5,80±4,56 e 5,14±3,82 anos), respectivamente. Os pacientes com lipodistrofia autorreferida tiveram maior alteração na distribuição da gordura corporal entre 3-6 anos de diagnóstico do HIV e um perfil colesterolêmico negativo. O tempo de tratamento com antirretroviral influenciou o colesterol total e os triglicerídeos, mesmo para os pacientes sem lipodistrofia autorreferida, com mais de nove anos sob tratamento. CONCLUSÃO Neste estudo, o perfil colesterolêmico negativo se relacionou principalmente ao tempo de tratamento com antirretroviral, mesmo para os pacientes sem lipodistrofia autorreferida e as alterações na distribuição da gordura corporal, mensuradas por antropometria, se associaram especialmente ao tempo de infecção pelo HIV naqueles com lipodistrofia autorreferida.

Memory impairment: an intermediate clinical syndrome symptom in HTLV-1-infected patients? / Comprometimento da memória: um sintoma de síndrome clínica intermediária em pacientes infectados pelo HTLV-1?

Background Although classical human T-cell lymphocyte virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis syndrome is the most frequent HTLV-1-associated neurological disorder, some "minor" neurological disorders can be seen in "asymptomatic" carriers. These disorders, including cognitive alterations already described in clinical cases and studies, may constitute an intermediate syndrome (IMS) between the asymptomatic state and myelopathy. The aim of this study was to investigate the presence of cognitive deficits in patients with HTLV-1 virus, who usually are diagnosed as asymptomatic. Methods A total of 54 HTLV-1-infected patients were evaluated, 35 asymptomatic and 19 with minor neurological alterations (evaluated by a neurologist); 25 HTLV-1-seronegative individuals served as controls. The instruments used were: Beck's Depression Inventory, Lawton's Daily Life Activity Scale, and a complete neuropsychological battery. The application of these evaluation instruments was performed blindly, with the evaluator neuropsychologist not knowing the clinical condition of the patient. Results Most of the participants in this cohort, including seronegative controls, were female (n = 57, 72.21%), their mean age was 52.34 years (SD = 14.29) and their average schooling was 9.70 years (SD = 4.11). Discussion Participants classified with IMS had lower gross scores when compared with both the patients classified as asymptomatic and with the control group, and when tested for auditory episodic memory of immediate (p < 0.01), and late (p = 0.01), recall. Conclusion Patients with IMS presented with memory impairment when compared with asymptomatic patients and seronegative individuals; this is one of the symptoms that aids in the classification of the syndrome.

RESUMO Apesar da síndrome de HAM / TSP clássica ser a perturbação neurológica mais atribuída, alguns distúrbios neurológicos denominados "menores" são vistos em portadores "assintomáticos" de HTLV-1. Esses distúrbios, incluindo alterações cognitivas já observadas em descrições de casos clínicos e estudos, podendo constituir uma verdadeira síndrome clínica intermediária (SI) entre o estado assintomático e mielopatia. O objetivo deste estudo foi investigar a presença de déficits cognitivos em pacientes portadores do vírus HTLV-1 diagnosticados classicamente como assintomáticos. Métodos Foram avaliadas 54 pessoas, sendo 35 assintomáticos, 19 com alterações neurológicas menores (avaliados por um neurologista) e 25 HTLV-1 negativo. Os instrumentos utilizados foram: Inventário Beck de Depressão, Escala de Atividades de Vida Diária de Lawton e uma completa bateria neuropsicológica. A aplicação destes instrumentos de avaliação foi realizada de forma cega, ou seja, a avaliadora não sabia a condição clinica do paciente. Resultados A maioria dos participantes era do sexo feminino (n = 57, 72,21%), com idade média de 52.34 anos (DP = 14,29) e escolaridade média de 9.70 anos (DP = 4,11). Discussão Avaliando o desempenho cognitivo nos três grupos, foi possível observar que os participantes classificados com SI, apresentaram menores escores brutos, quando comparados, com os pacientes com classificação assintomática e grupo controle e, em relação à memória episódica auditiva de evocação imediata (p < 0,01) (p = 0,01) e tardia. Conclusão Diante dos resultados foi possível concluir que os pacientes com SI apresentam comprometimento de memória quando comparado com os outros grupos, sendo possível, ser este um dos sintomas para auxiliar na classificação da síndrome.

The Th1-th2 profile in immune responses to Human papillomavirus (HPV) in vitro in men from the city of São Paulo, Brazil / Perfil Th1-Th2 nas respostas imunes ao Papilomavírus Humano (HPV) in vitro em homens da cidade de São Paulo, Brasil

Introduction: The cell-mediated immune response plays an important role in the control of HPV-induced cancers. Cytokines play an important function in host defense against HPV infection by modulating viral infection and polarizing the immune response towards Th1 or Th2 cells. Objective: To evaluate the specific immune response to HPV in vitro in men with and without lesions caused by HPV. Methods: We recruited 31 patients and 11 volunteers and divided them into the following four groups: 12 patients in Group A (HIV+/HPV+); 9 patients in Group B (HIV-/HPV+); 10 patients in Group C (HIV+/ HPV-); and 11 healthy subjects in Group D (HIV-/HPV-). PBMCs culture assays were performed to measure the levels of Th1/Th2/Th17 cytokines (IFN-γ, IL-2, TNF-α, IL-4, IL-10 and IL-17) in cells from patients stimulated with a quadrivalent HPV vaccine (HPV 6, 11, 16 and 18) and the E7 protein of HPV16. Results: The coinfected group A (HIV+/HPV+) showed higher levels of cytokines, especially Th2 cytokines, compared with the other study groups. The coinfected group had significantly higher levels of IL-6 and IL-10, which are Th2 cytokines, compared to the control group (HIV-/HPV-) (p<0.0001 and p<0.0001, respectively). Conclusion: This study reports a high production of cytokines in the coinfected group, suggesting strong immunomodulatory effects by HIV/HPV coinfection. However, further studies should be conducted to confirm these data. Because this group had high levels of Th2 cytokines, especially IL-6 and IL-10, these data suggest that these two cytokines may serve as biomarkers for viral persistence because HIV seropositive patients have a higher HPV persistence and may allow for the progression to more serious injuries to be monitored.

Introdução: A resposta imune celular exerce um importante papel no controle dos cânceres induzidos pela infecção por HPV. As citocinas desempenham um papel importante na defesa do hospedeiro contra a infecção pelo HPV pela modulação da infecção viral e a polarização da resposta imune para células Th1 ou Th2. Objetivo: Avaliar a resposta imune específica in vitro ao HPV em homens com e sem lesões causadas pelo HPV. Métodos: Foram recrutados 31 pacientes e 11 voluntários, divididos em quatro grupos: 12 pacientes no grupo A (HIV+/HPV+); 9 pacientes no grupo B (HIV-/HPV+); 10 pacientes no Grupo C (HIV+/HIV-); e 11 sujeitos saudáveis no grupo D (HIV-/HPV-). Uma cultura de PBMCs foi realizada para medir os níveis de citocinas Th1/ Th2/Th17 (IFN-γ, IL-2, TNF-α, IL-4, IL-10 e IL-17) de células de pacientes estimulados com a vacina quadrivalente para HPV (HPV 6, 11, 16 e 18) e a proteína E7 de HPV-16. Resultados: O grupo A coinfectado (HIV+/HIV+) apresentou altos níveis de citocinas, especialmente citocinas do perfil Th2, comparados com os demais grupos estudados. O grupo coinfectado apresentou níveis significativamente mais elevados de IL-6 e IL-10, citocinas do perfil Th2, comparados ao grupo controle (HIV-/HPV-) (p<0,0001 e p<0,0001, respectivamente). Conclusão: Este estudo reportou uma elevada produção de citocinas no grupo de coinfectados, sugerindo um forte efeito imunomodulatório pela coinfecção HIV/HPV. Entretanto, outros estudos devem ser conduzidos para confirmar estes dados. Devido este grupo apresentar altos níveis de citocinas Th2, especialmente IL-6 e IL-10, esses dados sugerem que essas duas citocinas podem servir como biomarcadores para a persistência viral, uma vez que pacientes soropositivos para HIV apresentam níveis mais altos de persistência pelo HPV e podem permitir que a progressão para lesões mais graves possa ser monitorada.

Moderada endemicidade da infecção pelo vírus linfotrópico-T humano na região metropolitana de Belém, Pará, Brasil / Moderate endemicity of the human T-lymphotropic virus infection in the metropolitan region of Belém, Pará, Brazil

RESUMO: Introdução: A disseminação da infecção pelo vírus linfotrópico-T humano (HTLV) em famílias da área metropolitana de Belém, Pará, Brasil, e a ausência de estudos na população em geral requisitam investigações que esclareçam melhor a sua prevalência na região. Metodologia: Foi realizada pesquisa de anticorpos anti-HTLV-1/HTLV-2 em indivíduos adultos transeuntes de logradouros públicos de Belém, entre novembro de 2014 e novembro de 2015. A infecção foi confirmada por pesquisa de DNA proviral e foi realizada avaliação clínica e investigação intrafamiliar dos infectados. Resultados: Dos 1.059 indivíduos investigados, 21 (2,0%) apresentaram amostras sororeagentes, 15 (1,4%) confirmados para HTLV-1, 5 (0,5%) para HTLV-2 e o DNA proviral foi indetectável em 1 caso. A média de idade dos infectados (57,2) foi maior que a dos não infectados (46,2) (p = 0,0010). A infecção aumentou com a idade e se destacou nos indivíduos com renda familiar menor ou igual a um salário mínimo. A transmissão intrafamiliar parece ter ocorrido em todas as famílias investigadas. Dentre os portadores de HTLV-1, 30% (3/10) já apresentavam algum sintoma relacionado à infecção. Discussão: O aumento da infecção de acordo com a idade pode ocorrer por soroconversão tardia de infecção pré-adquirida ou pelo risco cumulativo de novas infecções, sobretudo em mulheres. Conclusão: A infecção por HTLV demonstrou moderada prevalência na população estudada, com predomínio do HTLV-1. Essa mostrou-se associada à baixa renda e ao aumento da idade das mulheres. Também apresentou disseminação intrafamiliar e negligência no diagnóstico das doenças associadas.

ABSTRACT: Introduction: The spread of the HTLV infection in families living in the metropolitan area of Belém, Pará, Brazil, and the lack of studies in the general population requires studies to better understand its prevalence in the region. Methods: An anti-HTLV-1/HTLV-2 antibodies test was carried out on random adults in public places in Belém between November 2014 and November 2015. A proviral DNA test detected if the person was infected, and then a clinical evaluation and an intrafamilial investigation were carried out. Results: Of the 1059 individuals being investigated, 21 (2.0%) had seroreagent samples, 15 (1.4%) had HTLV-1, 5 (0.5%) had HTLV-2, and proviral DNA was undetectable in one case. The mean age of the infected people (57.2) was higher than that of those that were uninfected (46.2) (p = 0.0010). The prevalence of infection increased with age, especially in individuals with a family income equal to or less than a minimum wage. Intrafamilial transmission seems to have occurred in all of the families being studied. Among the patients with HTLV-1, 30% (3/10) already had some symptom related to the infection. Discussion: The increase in prevalence rates according to age may be due to late seroconversion of a previously acquired infection, or the cumulative risk of new infections, especially in women. Conclusion: There was a moderate prevalence of the HTLV infection among adult individuals from the metropolitan area of Belém, with a predominance of HTLV-1. This infection was associated with low income and increasingly older women. It also presented intrafamily spread and negligence in the diagnosis of associated diseases.

Depression and adherence to antiretroviral treatment in HIV-positive men in São Paulo, the largest city in South America: Social and psychological implications

OBJECTIVES: The aim of the present study was to investigate the prevalence of depression and adherence to antiretroviral treatment in two groups of individuals: men who have sex with men (MSM) and men who have sex with women (MSW). METHODS: Two hundred and sixteen participants (MSM=116; MSW=100) who visited the Clinics Hospital of the School of the Medicine of the University of São Paulo completed two independent surveys (the BECK Depression Inventory and an adherence self-declared questionnaire) to evaluate their depression status and adherence to antiretroviral treatment, respectively. RESULTS: The study highlighted a positive relationship between depression and low adherence to Highly Active Antiretroviral Therapy in these patients regardless of age and sexual orientation. In addition, MSM subjects were two times more prone than MSW subjects to develop depression symptoms. White or mixed race men showed 7.6 times greater adherence to treatment than black men. The probability of complete adherence to treatment was 3.8 times higher in non-depressed subjects than in depressed subjects regardless of their ethnicity. The chance of developing depression was 4.17 times higher for an individual with non-adherent behavior than for an adherent individual. CONCLUSIONS: Individuals with low adherence rates have proportionally higher depression rates. Depressed men tend to show less adherence to treatment. Black but not mixed race or white men show less adherence to Highly Active Antiretroviral Therapy and have a greater chance of developing depression, which directly interferes with adherence. The chances of developing depression are four times greater for a patient with non-adherent behavior than for a patient with adherent behavior.

Depression is inversely associated with sexual satisfaction and physical function in men living with HIV/AIDS / A depressão associa-se inversamente com satisfação o sexual e função física em homens positivos para HIV/AIDS

OBJECTIVE: To assess the associations between depression and physical fitness and function in men living with HIV/AIDS and the role of sexual satisfaction in these associations. DESIGN: Cross-sectional study conducted with 40 males living with HIV/AIDS (40.75 ± 8.68 years [25-66 yrs. old]) divided in two groups based on CD4+ nadir (low nadir < 200 cells/mm3; high nadir ≥ 200 cells/mm3). METHODS: Depression was determined by the Beck Depression Inventory. Participants were asked to evaluate their satisfaction with sexual life and their physical fitness was assessed by flexibility, muscle strength and peak oxygen uptake (VO2peak). Physical function was measured by time taken to move from seated to standing position (TSSP), time to tie sneakers, and time to walk 3.33 m. RESULTS: Depression was inversely associated with sexual satisfaction (for low and high CD4+ nadir) and flexibility (for low CD4+ nadir), and positively associated with walking time (for low CD4+ nadir and total sample), and time to tie sneakers (for the total sample). Sexual satisfaction was positively associated with muscle strength (for low CD4+ nadir and total sample), but inversely with TSSP (for low CD4+ nadir and total sample), walking time (for low CD4+ nadir and total sample), and time to tie sneakers (for high CD4+ nadir and total sample). CONCLUSION: Findings suggest a negative association between depression and physical function regardless of retrospective clinical status of men living with HIV/AIDS and a potential role for sexual satisfaction in explaining this association.

OBJETIVO: Analisar as associações entre depressão e aptidão e função físicas em homens vivendo com HIV/AIDS, e o papel da satisfação sexual nessas associações. MÉTODOS: Estudo transversal conduzido com 40 homens vivendo com HIV/AIDS (40,75 ± 8,68 anos [25-66 anos de idade]) divididos em dois grupos de acordo com o nadir de CD4+ (nadir baixo < 200 células/mm3; nadir alto ≥ 200 células/mm3). A depressão foi estimada pelo inventário de depressão de Beck. Os participantes auto-classificaram sua satisfação sexual. A aptidão física foi avaliada por meio da flexibilidade, força muscular e consumo de oxigênio de pico (VO2pico). A função física foi mensurada pelo tempo para levantar-se de uma posição sentada (TLPS), tempo para amarrar o tênis, e tempo para caminhar 3,33 m. RESULTADOS: A depressão foi inversamente associada com satisfação sexual (para nadir baixo e alto) e flexibilidade (para nadir baixo), e positivamente associada com tempo de caminhada (para nadir baixo e amostra total), e tempo para calçar e amarrar o tênis (amostra total). A satisfação sexual foi positivamente associada com força muscular (para nadir alto e amostra total), mas inversamente com TLPS (para nadir baixo e amostra total), tempo de caminhada (para nadir baixo e amostra total), e tempo para calçar e amarrar o tênis (para nadir alto e amostra total). CONCLUSÃO: Os dados sugerem que existe associação negativa entre depressão e função física independente do quadro clinico retrospectivo de homens vivendo com HIV/AIDS, e que parece existir, potencialmente, um papel para a satisfação sexual como explicação para essa associação.

Discordance beteeen body mass index and anthropmetric measurements among hiv-11-infected patients on antiretroviral therapy and with lipoatrophy/lipohypertrophy syndrome / Discordância entre o índice de massa corporal e outras medidas antropométricas em pacientes infectados pelo HIV com a síndrome de lipoatrofia/lipohipertrofia em uso de medicação antirretroviral

Introduction: Highly Active Antiretroviral Therapy (HAART) has improved and extended the lives of thousands of people living with HIV/AIDS around the world. However, this treatment can lead to the development of adverse reactions such as lipoatrophy/lipohypertrophy syndrome (LLS) and its associated risks. Objective: This study was designed to assess the prevalence of self-reported lipodystrophy and nutritional status by anthropometric measurements in patients with HIV/AIDS. Methods: An observational study of 227 adult patients in the Secondary Immunodeficiencies Outpatient Department of Dermatology, Hospital das Clínicas, Faculty of Medicine, University of São Paulo (3002 ADEE-HCFMUSP). The sample was divided into three groups; Group 1 = 92 patients on HAART and with self-reported lipodystrophy, Group 2 = 70 patients on HAART without self-reported lipodystrophy and Group 3 = 65 patients not taking HAART. The nutritional status of individuals in the study sample was determined by body mass index (BMI) and percentage of body fat (% BF). The cardiovascular risk and diseases associated with abdominal obesity were determined by waist/hip ratio (WHR) and waist circumference (WC). Results: The prevalence of self-reported lipoatrophy/lipohypertrophy syndrome was 33% among women and 59% among men. Anthropometry showed depletion of fat mass in the evaluation of the triceps (TSF) in the treatment groups with HAART and was statistically independent of gender; for men p = 0.001, and for women p = 0.007. Similar results were found in the measurement of skin folds of the upper and lower body (p = 0.001 and p = 0.003 respectively). In assessing the nutritional status of groups by BMI and % BF, excess weight and body fat were more prevalent among women compared to men (p = 0.726). The WHR and WC revealed risks for cardiovascular and other diseases associated with abdominal obesity for women on HAART and with self-reported LLS (p = 0.005) and (p = 0.011). ...

Objetivos: A terapia antirretroviral altamente ativa (HAART) tem melhorado e aumentado a vida de milhares de pessoas que vivem com a infecção pelo HIV/AIDS em todo o mundo. No entanto, este tratamento pode levar ao desenvolvimento da síndrome da lipodistrofia (LDS). Este estudo foi desenvolvido para avaliar a prevalência de auto-relato de LDS, perfil nutricional e medidas antropométricas de pacientes com HIV/AIDS. Métodos: Estudo observacional de 227 pacientes adultos, divididos em: Grupo 1: 92 pacientes em HAART e com LDS; Grupo 2: 70 pacientes em tratamento com HAART e sem LDS e Grupo 3: 65 pacientes que não tomam HAART. O estado nutricional foi avaliado pelo índice de massa corporal (IMC) e o percentual de gordura corporal (%GC) por meio de medidas antropométricas. Resultados: A prevalência de auto-relato de LDS foi de 44% entre as mulheres e 39% entre os homens. DC do tríceps (PCT) apresentou-se mais elevada no grupo HAART e LDS (homens p < 0,001; mulheres p < 0,007) em comparação com aqueles sem HAART, respectivamente. IMC revelou excesso de peso para a maioria dos indivíduos. Conclusões: As medidas antropométricas foram úteis para confirmar a prevalência de auto-relato da síndrome da lipodistrofia. A avaliação das dobras dos braços e pernas revelou-se um bom método para avaliação antropométrica de lipoatrofia de membro, independentemente do sexo. Estes resultados permitiram o estabelecimento de estratégias para o diagnóstico precoce da LDS na prática clínica, em pessoas vivendo com HIV / AIDS. .

Origin and prevllence of human t-lymphotropic vrus type 1 (htlv-1) and type 2 (htlv-2) among indigenous populations in the americas / Origem e prevalência do vírus linfotrópico de células T humanas em populações indígenas das Américas

Human T-lymphotropic virus type 1 (HTLV-1) is found in indigenous peoples of the Pacific Islands and the Americas, whereas type 2 (HTLV-2) is widely distributed among the indigenous peoples of the Americas, where it appears to be more prevalent than HTLV-1, and in some tribes of Central Africa. HTLV-2 is considered ancestral in the Americas and is transmitted to the general population and injection drug users from the indigenous population. In the Americas, HTLV-1 has more than one origin, being brought by immigrants in the Paleolithic period through the Bering Strait, through slave trade during the colonial period, and through Japanese immigration from the early 20th century, whereas HTLV-2 was only brought by immigrants through the Bering Strait. The endemicity of HTLV-2 among the indigenous people of Brazil makes the Brazilian Amazon the largest endemic area in the world for its occurrence. A review of HTLV-1 in all Brazilian tribes supports the African origin of HTLV-1 in Brazil. The risk of hyperendemicity in these epidemiologically closed populations and transmission to other populations reinforces the importance of public health interventions for HTLV control, including the recognition of the infection among reportable diseases and events.

O vírus linfotrópico de células T humanas do tipo 1 (HTLV-1) é encontrado em populações indígenas de países do Pacífico e Américas enquanto o tipo 2 (HTLV-2) é amplamente distribuído entre as populações indígenas das Américas, nas quais aparenta ser mais prevalente que o HTLV-1, e em algumas tribos da África Central, sendo considerado ancestral nas Américas e transmitido à população geral e de usuários de drogas injetáveis a partir da população indígena. No continente americano o HTLV-1 teria mais de uma origem, sendo trazido na era paleolítica pelos imigrantes através do estreito de Bering, através do tráfico de escravos no período colonial e com a imigração japonesa a partir do início do século XX, enquanto para o HTLV-2 teria sido trazido pelos imigrantes através do estreito de Bering. A endemicidade do HTLV-2 entre os indígenas do Brasil tornam a região amazônica brasileira a maior área endêmica do mundo para sua ocorrência e a revisão da infecção pelo HTLV-1 em todas as tribos brasileiras apoiam a origem africana do HTLV-1 no Brasil. O risco de hiperendemicidade nestas populações epidemiologicamente fechadas e de transmissão a outras populações reforçam a importância de medidas no âmbito da saúde pública para seu controle, incluindo o reconhecimento da infecção entre os agravos e eventos de notificação compulsória.

Determination o viral tropism by genotyping an phenotyping assays in Braziliaan hiv-1-infected patients / Determinação do tropismo viral por ensaios genotípicos e fenotípicos em pacientes brasileiros infectados por HIV-1

The clinical application of CCR5 antagonists involves first determining the coreceptor usage by the infecting viral strain. Bioinformatics programs that predict coreceptor usage could provide an alternative method to screen candidates for treatment with CCR5 antagonists, particularly in countries with limited financial resources. Thus, the present study aims to identify the best approach using bioinformatics tools for determining HIV-1 coreceptor usage in clinical practice. Proviral DNA sequences and Trofile results from 99 HIV-1-infected subjects under clinical monitoring were analyzed in this study. Based on the Trofile results, the viral variants present were 81.1% R5, 21.4% R5X4 and 1.8% X4. Determination of tropism using a Geno2pheno[coreceptor] analysis with a false positive rate of 10% gave the most suitable performance in this sampling: the R5 and X4 strains were found at frequencies of 78.5% and 28.4%, respectively, and there was 78.6% concordance between the phenotypic and genotypic results. Further studies are needed to clarify how genetic diversity amongst virus strains affects bioinformatics-driven approaches for determining tropism. Although this strategy could be useful for screening patients in developing countries, some limitations remain that restrict the wider application of coreceptor usage tests in clinical practice.

A aplicação clínica dos antagonistas de CCR5 envolve em primeiro lugar determinar o uso de co-receptor pela cepa viral infectante. Programas de bioinformática que prevêem o uso co-receptor poderiam fornecer um método alternativo para selecionar candidatos para o tratamento com os antagonistas do CCR5, particularmente em países com poucos recursos financeiros. Assim, o presente estudo teve por objetivo identificar a melhor abordagem utilizando ferramentas de bioinformática para determinar qual o tipo de co-receptor do HIV-1 que poderia ser usado na prática clínica. Sequências de DNA proviral e Trofile resultados a partir de 99 pacientes infectados pelo HIV-1 sob monitorização clínica foram avaliadas. Com base nos resultados do Teste Trofile, as variantes virais presentes eram R5 (81,1%), R5X4 (21,4%) e X4 (1,8%). Determinação do tropismo pela análise do Geno2pheno, com taxa de falso positivos de 10% apresentou desempenho mais adequado para esta amostragem: as cepas R5 e X4 foram encontradas em frequências de 78,5% e 28,4%, respectivamente, e foi de 78,6% a concordância entre os resultados fenotípicos e genotípicos. Mais estudos são necessários para esclarecer como a diversidade genética entre as cepas do vírus afeta abordagens baseadas na determinação do tropismo pelas ferramentas de bioinformática. Embora esta estratégia possa ser útil para o rastreio de pacientes em países em desenvolvimento, permanecem algumas limitações que restringem a aplicação mais ampla para utilização de testes de co-receptor na prática clínica.

Sexual transmission of human T-cell lymphotropic virus type 1

Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in many parts of the world and is primarily transmitted through sexual intercourse or from mother to child. Sexual transmission occurs more efficiently from men to women than women to men and might be enhanced by sexually transmitted diseases that cause ulcers and result in mucosal ruptures, such as syphilis, herpes simplex type 2 (HSV-2), and chancroid. Other sexually transmitted diseases might result in the recruitment of inflammatory cells and could increase the risk of HTLV-1 acquisition and transmission. Additionally, factors that are associated with higher transmission risks include the presence of antibodies against the viral oncoprotein Tax (anti-Tax), a higher proviral load in peripheral blood lymphocytes, and increased cervicovaginal or seminal secretions. Seminal fluid has been reported to increase HTLV replication and transmission, whereas male circumcision and neutralizing antibodies might have a protective effect. Recently, free virions were discovered in plasma, which reveals a possible new mode of HTLV replication. It is unclear how this discovery might affect the routes of HTLV transmission, particularly sexual transmission, because HTLV transmission rates are significantly higher from men to women than women to men.

Association between muscle strength and the cardiopulmonary status of individuals living with HIV/AIDS

OBJECTIVE: The purpose of this study was to compare aerobic function [anaerobic threshold (%VO2-AT), respiratory compensation point (%VO2-RCP) and peak oxygen uptake (VO2peak)] between physically active patients with HIV/AIDS and matched controls and to examine associations between disease status, poor muscle strength, depression (as estimated by the profile of mood states questionnaire) and the aerobic performance of patients. METHODS: Progressive treadmill test data for %VO2-AT (V-slope method), RCP and (VO2peak) were compared between 39 male patients with HIV/AIDS (age 40.6±1.4 years) and 28 male controls (age 44.4±2.1 years) drawn from the same community and matched for habitual physical activity. Within-patient data were also examined in relation to CD4+ counts (nadir and current data) and peak isokinetic knee torque. RESULTS: AT, RCP and (VO2peak) values were generally similar for patients and controls.Within the patient sample, binary classification suggested that AT, RCP and (VO2peak) values were not associated with either the nadir or current CD4+ count, but treadmill test variables were positively associated with peak isokinetic knee torque. CONCLUSION: The aerobic performance of physically active patients with HIV/AIDS is generally well conserved. Nevertheless, poor muscle strength is observed in some HIV/AIDS patients, which is associated with lower anaerobic power and (VO2peak), suggesting the possibility of enhancing the aerobic performance of patients with weak muscles through appropriate muscle-strengthening activities.

Tuberculosis among HIV-1-infected subjects in a tertiary out-patient service in São Paulo city, Brazil / Tuberculose entre pacientes infectados pelo HIV-1 em ambulatório terciário de São Paulo, Brasil

TB is currently considered to be the most important infectious disease among HIV-1-infected subjects in developing countries, such as Brazil. A retrospective analysis of TB cases was performed, occurring from January 1995 to December 2010 in our cohort of 599 HIV positive patients. The primary outcome was the occurrence of active TB. Forty-one TB cases were diagnosed over this period of 16 years, among 599 HIV positive patients in an open cohort setting in the city of Sao Paulo, Brazil. All-time lowest mean CD4 T cell count at the time of TB diagnosis was 146 and 186 cells/mm³, respectively. The mean HIV viral load was 5.19 log10 copies/mL, and 59% of the patients were on HAART. TB incidence was 1.47 per 100 person-years, for a total follow-up time of 2775 person-years. The probability of surviving up to 10 years after diagnosis was 75% for TB patients as opposed to 96% for patients with other, non-TB opportunistic diseases (p = 0.03). TB can be considered a public health problem among people living with HIV in Brazil despite of the widespread use of antiretrovirals for the treatment of HIV infection/AIDS.

Atualmente, a tuberculose (TB) é considerada a doença infecciosa mais importante entre os pacientes infectados pelo HIV-1 nos países em desenvolvimento, como o Brasil. Análise retrospectiva dos casos de tuberculose ocorridos a partir de janeiro 1995 até dezembro de 2010 foi realizada em nossa coorte de 599 pacientes HIV positivos. O desfecho primário foi a ocorrência de TB ativa, e 41 casos da doença foram diagnosticados durante este período de 16 anos. As contagens médias do nadir de células T CD4 e ao momento do diagnóstico de TB foram de 146 e 217 células/mm³, respectivamente. A carga viral média de HIV foi de 5,19 log10 cópias/mL, e 59% dos pacientes estavam em tratamento com ART. A incidência de TB foi de 1,47 casos por 100 pessoas-ano, para um tempo total de seguimento da coorte de 2775 pessoas-ano. A probabilidade de sobreviver até 10 anos após o diagnóstico foi de 75% para pacientes com TB, em oposição a 96% para pacientes com outras doenças oportunistas não-TB (p = 0,03). A tuberculose pode ser considerada problema de saúde pública entre as pessoas que vivem com HIV no Brasil, apesar da ampla utilização de anti-retrovirais para o tratamento da infecção pelo HIV / AIDS.

Prevalence of anxiety, depression and quality of life in HTLV-1 infected patients

The HAM/TSP caused by HTLV-1 infection usually affects patients to disabling states, and sometimes can lead them to paraplegia presenting symptoms of depression and anxiety, impacting on quality of life. Objective: The purpose of this study was to evaluate the frequency of depression and anxiety and its impact on quality of life in HTLV-1-infected TSP/HAM patients. Material and Methods: This was a cross-sectional study including 67 asymptomatic (control group) and 63 with TSP/HAM subjects. The instruments used were a demographic questionnaire, scales for anxiety and depression diagnosis (BDI and BAI), questionnaire for the assessment of Quality of Life of the World Health Organization (WHOQOL-Brief) and neurological scale to measure the disability level (Osame's Disability Status Scale). All patients had HTLV-I diagnosis by serological and molecular approaches, monitored at Instituto de Infectologia Emílio Ribas from May 2008 to July 2009. Data were analyzed statistically by frequencies, the Mann-Whitney test and the Spearman correlation test. Data among groups were analyzed and correlated with functional and severity aspects. Results: The results showed that patients with HAM/TSP compared to asymptomatic carriers had higher rates of depression (p < 0.001) and anxiety (p < 0.001), and impairment on quality of life in the areas of: dissatisfaction with health (p < 0.001), physical (p < 0.001) and the environment (p = 0.003). The main factors that correlated with levels of depression and anxiety and the domains of the WHOQOL-brief were: education, family income and social class. Conclusion: A well conducted evaluation and counseling may help in treatment, for a better quality of life of these patients.