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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.

Few studies have reported the prognosis of human immunodeficiency virus (HIV)-positive patients followed for a long time in Brazil, particularly those including pre and post-HAART eras. The polymorphisms of interferon (IFN)-λ4 have been postulated as possibly associated with the pathogenesis of HIV infection. The aim of this study was to describe the incidence and mortality from a cohort of HIV-positive patients as well as whether IFN-λ4 gene polymorphisms (SNP rs8099917 and SNP rs12979860) were associated with HIV/acquired immune deficiency syndrome (AIDS) progression. We followed 402 patients for up to 30 years; 347 of them began follow-up asymptomatic, without any AIDS-defining opportunistic disease and/or a lymphocytes T CD4+ count of 350 cells/mm3 or lower. We determined the probability of the asymptomatic subjects to remain AIDS-free, and the risk of death for those entering the study already with an AIDS diagnosis, as well as for subjects developing AIDS during follow-up. We compared the prognosis of patients with two different polymorphisms for the genes encoding for IFN-λ4, variants rs8099917 and rs12979860. The follow-up time of the 347 asymptomatic-at-entry subjects was 3687 person-years. IFN-λ4 rs8099917 polymorphisms were not associated with AIDS progression, but IFN-λ4 rs12979860 wild type genotype (CC) was associated with higher mortality compared to CT and TT, with an increased probability of death from AIDS (P = .01). In conclusion, genetic variations in IFN-λ4 on rs12979860 polymorphisms in HIV-infected patients may drive mortality risk.

Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed.

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

BackgroundHuman T-cell lymphotropic virus type 1 (HTLV-1) infection is associated not only with some severe manifestations, such as HTLV-1-associated myelopathy (HAM) and ATLL, but also with other, less severe conditions. Some studies have reported neurologic manifestations that did not meet all the criteria for the diagnosis of HAM in individuals infected with HTLV-1; these conditions may later progress to HAM or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. This study evaluated the prognostic value and looked for a possible association of those parameters with the intermediate syndrome (IS) status and HAM status.MethodsProviral load (PVL), spontaneous lymphoproliferation, interferon (IFN)-γ spontaneous production was quantified in samples of asymptomatic and HAM patients, as well as patients with IS.ResultsThe critical age range was 50–60 years for IS outcome and more of 60 years for HAM outcome, with an increased risk of 2.5-fold for IS and 6.8-fold for HAM. IFN-γ was increased in patients with IS compared with asymptomatic carriers (ACs) (p = 0.007) and in patients with HAM compared with ACs (p = 0.03). Lymphoproliferation was increased in patients with HAM vs ACs (p = 0.0001) and patients with IS (p = 0.0001). PVL was similar between groups.ConclusionIFN-γ has high specificity of prediction of subject remain asymptomatic compared with PVL and lymphoproliferation assay tests. IFN-γ has been shown to be a biomarker of progression to intermediate stage and to HAM. The association of other markers with manifestations associated with HTLV-1 infection that does not meet the HAM criteria should be verified.

BackgroundHTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit.ObjectiveTo investigate systemic cytokines and GlycA as possible biomarkers of immunopathogenesis and therapeutic response to corticosteroid pulse therapy in HAM/TSP.MethodsWe prospectively followed 110 People living with HTLV-1 (PLwHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients), for a total of 906 person-years. Plasma cytokine levels (IL-2/4/6/10/17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and 1NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We applied logistic regression and machine learning algorithms to predict disease progression and glucocorticoid response.ResultsIL-6 was positively correlated with age and GlycA in asymptomatics but not HAM/TSP patients. Systemic IFN-γ and IL-17A levels were increased in HAM/TSP patients, as compared to asymptomatics. All patients significantly decreased IL-17A levels post-treatment but only prednisolone-responders decreased IFN-γ levels post-treatment. Higher pre-treatment GlycA and TNF levels significantly predicted a negative therapeutic outcome, which was associated with higher post-treatment IFN-γ levels. Low IL-4 and IL-10 levels in incident HAM/TSP can be reverted to increased IL-10 and IL-4/IL-13 signaling by prednisolone in vitro.Conclusions1) An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLwHTLV-1. 2) IFN-γ and IL-17A are biomarkers of untreated, active HAM/TSP disease, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy. 3) Low IL-4/IL-10 and high IFN-γ signaling in incident HAM/TSP can be normalized by prednisolone.

Background: Central nervous system involvement associated with Coronavirus Disease 2019 (COVID-19) has been reported, including cognitive impairment, even in patients with mild COVID-19. processes. Objective: To assess cognitive decline related to the SARS-CoV-2 infection in patients with neurological disease after COVID-19. Methods: Longitudinal prospective study developed to compare the cognitive performance of patients after COVID-19 based on cognitive complaints. The Addenbrooke´s Cognitive ExaminationRevised (ACE-R), a 100-point test, was applied for investigation, with cut-off score for cognitively normal individuals ≥ 78. Results: Fifty patients were evaluated, 33 women (66%). Thirty-six patients with cognitive complaint (72%), this being the only symptom in 18 (50%), more frequent in women (5:1). Among all patients, the mean score of ACE-R was 80.8 (SD 11) and median of 84. In patients with cognitive complaints, mean of 80.37 (SD 12.2) and median of 84. For the other patients, mean of 81.86 (SD 7.65) and median of 82.5 (p value = 0.9869). Cognitive decline was confirmed in 10/35 (28.57%) of patients with cognitive complaint, and in 4/14 (28.57%) of other patients (exacto de Fisher = 0.8809). Regarding the ACE-R subanalyses, impaired attention and orientation were observed in both groups. Conclusion: Cognitive complaint was not a predictor of cognitive decline, but impairment in attention and orientation were observed in the entire sample.

BACKGROUND Long-term regular physical activity, such as body practices of Traditional Chinese Medicine, seems to be an important habit for maintaining the functional fitness, independence and quality of life of elderly individuals. However, scientific knowledge production concerning assessment of such practices, specifically for the elderly population, focusing on functional fitness and quality of life, is still modest. Moreover, there is a lack of studies with long-term follow-up and control groups. Therefore, this study aims to compare the parameters of functional fitness and the dimensions of quality of life of elderly participants and non-participants in the body practices of Traditional Chinese Medicine. Longer adherence time, shorter adherence time and control group have been considered. METHODS This is an observational epidemiological case-control study carried out with 118 elderly individuals (≥ 60 years). The case group was represented by 59 elderly people practicing the body practices of Traditional Chinese Medicine, and they were subdivided into two groups, according to their median adherence time (

Introduction Several genetic polymorphisms may be related to susceptibility or resistance to viral disease outcomes. Immunological or genetic factors may act as major triggers of the immune pathogenesis of HAM/TSP. This study investigated the association of immune related genetic polymorphisms with viral and immunological markers. Methods 247 HTLV-1-infected volunteers, drawn from a larger group of HTLV-infected subjects followed at the Institute of Infectious Diseases “Emilio Ribas” (IIER) for up to 19 years, participated in this study, which ran from June 2011 to July 2016. The subjects were classified according to their neurological status into two groups: Group 1 (160 asymptomatic individuals) and Group 2 (87 HAM/TSP patients). Samples were tested for spontaneous lymphocyte proliferation (LPA) and HTLV-1 proviral load (PVL) and for IFN-λ4, HLA-C and KIR genotypes using qPCR. Results We found associations between LPA (p = 0.0001) with HAM/TSP and confirmed the IFN-λ4 polymorphism rs8099917, allele GG, as a protective factor using a recessive model (OR = 3.22, CI = 1.10–9.47). Polymorphisms in HLA-C and KIR alleles were not associated with risk of developing HAM/TSP. Conclusion We demonstrated that age, LPA and an IFN-λ4 polymorphism were associated with progression to HAM/TSP. Understanding HAM/TSP pathogenesis can provide important markers of prognostic value for clinical management, and contribute to the discovery of new therapeutic interventions in the future.

Background: Despite its relatively low incidence of associated diseases, Human T-cell Leukemia Virus-1 (HTLV-1) infection was reported to carry a significant risk of mortality in several endemic areas. HTLV-1-associated diseases, adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraperesis (HAM/TSP), as well as frequent coinfections with human immunodeficiency virus (HIV), hepatitis C virus (HCV), and Strongyloides stercoralis were associated to increased morbidity and mortality of HTLV-1 infection. Objective: To determine the mortality rate and its associated variables from an open cohort started in July 1997 at the HTLV Clinic, Emilio Ribas Institute (IIER), a major infectious disease hospital in S&atilde, o Paulo, Brazil. Methods: Since inception up to September 2018, we admitted 727 HTLV-1-infected individuals, with a rate of 30&ndash, 50 new admissions per year. All patient data, including clinical and laboratory data, were regularly updated throughout the 21-year period, using a dedicated REDCap database. The Ethical Board of IIER approved the protocol. Results: During 21 years of clinical care to people living with HTLV-1 in the S&atilde, o Paulo region, we recruited 479 asymptomatic HTLV-1-infected individuals and 248 HAM/TSP patients, of which 632 remained under active follow-up. During a total of 3800 person-years of follow-up (maximum follow-up 21.5 years, mean follow-up 6.0 years), 27 individuals died (median age of 51.5 years), of which 12 were asymptomatic, one ATLL patient and 14 HAM/TSP patients. HAM/TSP diagnosis (but neither age nor gender) was a significant predictor of increased mortality by univariate and multivariate (hazard ratio (HR) 5.03, 95% CI [1.96&ndash, 12.91], p = 0.001) Cox regression models. Coinfection with HIV/HCV was an independent predictor of increased mortality (HR 15.08, 95% CI [5.50&ndash, 41.32], p &lt, 0.001), with AIDS-related infections as a more frequent cause of death in asymptomatics (6/13, p = 0.033). HIV/HCV-negative fatal HAM/TSP cases were all female, with urinary tract infection and decubitus ulcer-associated sepsis as the main cause of death (8/14, p = 0.002). Conclusions: All-cause mortality among people living with HTLV-1 in S&atilde, o Paulo differs between asymptomatic (2.9%) and HAM/TSP patients (7.3%), independent of age and gender. We observe a dichotomy in fatal cases, with HAM/TSP and HIV/HCV coinfection as independent risk factors for death. Our findings reveal an urgent need for public health actions, as the major causes of death, infections secondary to decubitus ulcers, and immune deficiency syndrome (AIDS)-related infections, can be targeted by preventive measures.

Human T-lymphotropic virus type 1 (HTLV-1) was the first retrovirus to be isolated in humans. At least 5–10 million individuals harbor the virus worldwide1. In Brazil, between 800,000 and 2.5 million individuals are infected with HTLV-11,2. The geographic distribution of infection is heterogenous in this country and more pronounced in the North and Northeast, mainly affecting low-income populations2,3. One of the few studies that attempted to estimate the prevalence of infection in a general population was conducted in the city of Salvador, reported to be approximately 1.8%3. Most studies involving Brazilian populations have been performed in specific groups, such as blood donors or pregnant women, and the prevalence in the overall population remains unknown4.

Several studies suggest that HTLV-1 infection may be associated with a wider spectrum of neurologic manifestations that do not meet diagnostic criteria for HAM/TSP. These conditions may later progress to HAM/TSP or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. Our aim was to determine the prevalence of HTLV-1-associated disease in subjects without HAM/TSP, and the relationship between these findings with HTLV-1 proviral load (PVL). Methods: 175 HTLV-1-infected subjects were submitted to a careful neurological evaluation, during their regular follow up at the HTLV outpatient clinic of the Institute of Infectious Diseases “Emilio Ribas”, São Paulo city, Brazil. Clinical evaluation and blinded standardized neurological screening were performed for all the subjects by the same neurologist (MH). Results: After the neurological evaluation, 133 patients were classified as asymptomatic and 42 fulfilled the criteria for intermediate syndrome (IS). The mean age of the enrolled subjects was 46.3 years and 130 (74.3%) were females. Clinical classification shows that neurological symptoms (p, Author summary At least 5–10 million people live with the Human T-Cell Lymphotropic Virus type 1 (HTLV-1) worldwide, and around 0.25–5% of them may develop HTLV-1-associated myelopathy/Tropical spastic paraparesis (HAM/TSP), which is associated with chronic inflammation. In this study, involving 175 HTLV-1-infected subjects originally classified as asymptomatic, we found that 42 of them in reality presented some early clinical conditions, including alterations related not only to the neurological system, but also to the eyes and the skin. We called such conditions intermediate syndrome. Thus, it seems reasonable to suggest that all HTLV-1-infected subjects should be monitored for symptoms that may arise earlier in the course of their infection.

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.

HTLV-1 is transmitted primarily either through sexual intercourse or from mother to child. The mother/child pairs were classified as seroconcordant or serodiscordant. We analyzed mother to child transmission (MTCT) according to sociodemographic, clinical and epidemiological characteristics of the mother, child’s gender and duration of breastfeeding. Between June 2006 and August 2016 we followed 192 mothers with HTLV-1 infection (mean age 41 years old), resulting in 499 exposed offspring, 288 (57.7%) of whom were tested for HTLV-1, making up the final sample for the study, along with their 134 respective mothers. Among the tested mother/child pairs, 41 (14.2%) were HTLV-1 positive, highlighted that seven of 134 family clusters concentrated 48.8% of positive cases. Variables associated with a positive child: breastfeeding duration ≥12 months, maternal PVL ≥100 copies/104 PBMC, mother’s age at delivery >26 years old, and HTLV-1 in more than one child of the same mother. In a multiple logistic regression, breastfeeding ≥12 months, higher maternal PVL and ≥2 previous HTLV-1-infected children remained independently associated with the outcome. Thus, high maternal PVL and breastfeeding beyond 12 months were independently associated with MTCT of the HTLV-1 infection. Our results reinforce the need for both prenatal HTLV screening in endemic areas and for advising mothers on breastfeeding.

Decrease in bone mineral density (BMD) has been a complication among people living with HIV/AIDS. To investigate the prevalence of osteopenia/osteoporosis among HIV-infected people living in São Paulo city, we studied 108 HIV-infected patients (79 men and 29 women). We extracted data from patients’ medical records and BMD was measured by dual-energy X-ray absorptiometry (DXA). Median age of participants was 42 years (interquartile range [IQR] 36-48 years), and the median time since HIV diagnosis was 4.01 years (IQR 2-11 years). Patients had acquired HIV primarily by the sexual route (men who have sex with men 44%, heterosexual 49%). Median age, duration of HIV infection, duration of ART and CD4 nadir were similar for men and women. Plasma viral load was undetectable for 53 patients (49%). Median CD4 T cell count was 399 cells/µL (IQR 247 - 568). Twenty five patients (23%) had LBMD, and there was no statistically significant difference between men and women (

Human T-cell lymphotropic virus type 1 is transmitted primarily either through sexual intercourse or from mother to child. The current study investigated sexual transmission and compared the HTLV-1 proviral load between seroconcordant and serodiscordant couples by examining both men and women among the index partners without using subjective criteria to establish the direction of sexual transmission. Between January 2013 and May 2015, 178 HTLV-1-positive patients had spouses, 107 of which had tested partners, thus increasing the initial sample size (46 men and 61 women). Individuals co-infected with HTLV-2 or human immunodeficiency virus were not included in the analysis. From among the included participants, 26 men and 26 women were paired with each other, resulting in 26 seroconcordant couples; 12 seroconcordant couples were formed from another four men and eight women. Forty-three serodiscordant couples were formed from 16 men and 27 women. The rate of seroconcordance was 46.9%. The HTLV-1 proviral load was compared between 19 and 37 seroconcordant and serodiscondant couples, respectively, and the concordant couples showed higher proviral loads (P = 0.03). There were no differences between the groups according to age, relationship length, having a mother or sibling with HTLV-1, race, ethnicity, nationality, education, history of blood transfusion, HAM/TSP, ALT, or hepatitis C virus status. In multivariate analysis, relationship time was shown associated with ocurrence of seroconcordance status. The apparent association between high circulating levels of provirus and seroconcordance rate among couples suggests that proviral loads contribute markedly to the risk of sexual transmission, regardless of gender index.

As doenças virais têm sido importantes causas de morbidade e mortalidade nas últimas décadas, sendo que algumas delas são relacionadas com polimorfismos genéticos, que determinam a susceptibilidade do hospedeiro ou a resistência a essas infecções, influenciando na patogênese, além de desempenhar importante papel em respostas ao tratamento. Entre elas, destaca-se o HTLV-1, sendo que cerca de 10 a 20 milhões de pessoas em todo o mundo possuem esse vírus. Apenas 5% dos indivíduos infectados desenvolverão algum tipo de doença relacionada a tal infecção, entre elas destaca-se a HAM/TSP. Apesar da complexidade, o entendimento das interações hospedeiro versus HTLV-1 é de fundamental importância para avaliar prognóstico clínico dos portadores assintomáticos, visto que as opções diagnósticas e de tratamento não são adequadas, até o momento, para determinar o risco de progressão para HAM/TSP. Com isso, este trabalho objetivou estudar a associação entre alguns marcadores virais, genéticos e imunológicos relacionados ao desenvolvimento de HAM/TSPem pacientes infectados por HTLV-1. O ambulatório de HTLV do Instituto de Infectologia \"Emilio Ribas\" (IIER) possui uma coorte de portadores de HTLV em seguimento há 19 anos, para o presente estudo foram selecionados 247 voluntários portadores de HTLV-1, por conveniência. Somente pacientes adultos, com seguimento ativo no ambulatório no período de junho de 2011 até julho de 2016 foram convidados a participar. Este protocolo foi aprovado pelo CEP do IIER (Nº13/2011), e o TCLE foi obtido de todos os voluntários participantes. Os indivíduos foram classificados de acordo com seu quadro clínico neurológico em dois grupos: Grupo I (160 assintomáticos) e Grupo II (87 HAM/TSP). Amostra de sangue venoso foi coletada e as células mononucleares separadas. O material foi utilizado para o ensaio de PVL e para a genotipagem de IFN-?4, HLA-C e KIR, pela técnica de qPCR . A análise estatística no modelo multivariado mostrou associação de risco para HAM/TSP com as variáveis LPA (p=0,001) e a idade (p=0,019), além disso, o polimorfismo doIFN-?4 no rs8099917 foi associado no modelo recessivo(OR=0,31, IC=0,105 - 0,961) como fator de proteção ao desfecho.:Esse modelo estudado explica 8% dos fatores de progressão e de proteção para HAM/TSP. Desse modo, estudos genéticos multicêntricos envolvendo análise de exoma e maior número de casos de HAM/TSP, deveriam ser realizados. O entendimento da patogênese da mielopatia pode oferecer marcadores de valor prognóstico importantes para o manejo clínico, além de contribuir para o achado de novas intervenções terapêuticas no futuro. The viral diseases have been major causes of morbidity and mortality in recent decades, some of which are related to genetic polymorphisms, which determine the susceptibility or resistance to these infections, influencing the pathogenesis, besides of playing an important role in responses to treatment. Among them, it is highlighted HTLV-1, in which around 10 to 20 million people worldwide. Only 5% of infected subjects will develop some kind of disease related to such infection, including HAM/TSP. Despite the complexity, the understanding of host interactions versus HTLV-1 is fundamental importance to evaluate clinical prognosis of asymptomatic subjects, once the diagnostic options and treatment are not adequate, so far, to determine the risk of progression to HAM/TSP. Therefore, the purpose of this study was to investigate the association among some genetic polymorphisms, viral and immunological markers related to the development of HAM/TSP in HTLV-1-infected subjects. At the Institute of Infectious Diseases \"Emilio Ribas\" (IIER) has a cohort of HTLV subjects followed up for 19 years, for this study 247 volunteers with HTLV-1were selected for convenience. Only adult patients with active follow up in the period from June 2011 to July 2016 were invited to participate. This protocol was approved by the ethical committee at IIER (nº13/2011), informed consent was obtained. Subjects were classified according to their neurological status in two groups: Group I (160 asymptomatic) and Group II (87 HAM / TSP). Blood sample was collected and PBMCs The DNA was used to the PVL assay and IFN-?4, HLA-C and KIR genotyping using qPCR. It has been observed an association to HAM/TSP with LPA variables (p=0.001) and age (p=0.019) in the multivariable analysis. On the other hand, the polymorphism of IFN-?4 rs8099917 was associated in the recessive model (OR=0.31, CI=0.105-0.961) as a protective factor to HAM/TSP. This study explains 8% of progression and protective factors for HAM/TSP. Thus, multi-center studies involving genetic analysis and more cases of HAM/TSP, should be done. The understanding of the HAM/TSP pathogenesis can provide important markers of prognostic value for clinical management and contribute to the discovery of new therapeutic interventions in the future.

Human T-cell leukemia virus type 1 (HTLV-1), hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are prevalent worldwide, and share similar means of transmission. These infections may influence each other in evolution and outcome, including cancer or immunodeficiency. Many studies have reported the influence of genetic markers on the host immune response against different persistent viral infections, such as HTLV-1 infection, pointing to the importance of the individual genetic background on their outcomes. However, despite recent advances on the knowledge of the pathogenesis of HTLV-1 infection, gaps in the understanding of the role of the individual genetic background on the progress to disease clinically manifested still remain. In this scenario, much less is known regarding the influence of genetic factors in the context of dual or triple infections or their influence on the underlying mechanisms that lead to outcomes that differ from those observed in monoinfection. This review describes the main factors involved in the virus–host balance, especially for some particular human leukocyte antigen (HLA) haplotypes, and other important genetic markers in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other persistent viruses, such as HIV and HCV.

O polimorfismo de IL28B foi descrito como fator importante na patogênese de infecções causadas por alguns vírus. O objetivo desta pesquisa foi avaliar se polimorfismos (SNP rs8099917 IL28B e SNP rs12979860) foram associados na presença de HAM/TSP. Métodos: O estudo incluiu 188 pacientes do Instituto de Infectologia \"Emilio Ribas\" de São Paulo, divididos em três grupos: 117 Indivíduos infectados pelo HTLV-1 (49 assintomáticos e 68 com HAM TSP), 47 Pacientes monoinfectados pelo vírus da Hepatite C (HCV) e 24 coinfectados pelo HTLV- 1 e HCV. Amostras de sangue foram coletadas, e o PBMC separado através da centrifugação por gradiente de densidade Ficoll-Hypaque. O DNA foi extraído usando um kit comercial, e armazenado a - 80 ° C e, a carga proviral do HTLV-1 foi quantificada. Os SNPs da IL28B na região rs8099917 e rs12979860 foram analisados em todos os grupos por PCR StepOnePlus. Resultados: A análise estatística usando modelo multivariado que incluiu as variáveis: gênero, idade, e carga proviral do HTLV-1, mostrando que o polimorfismo IL28B SNP rs12979860 não foi associado com a HAM/TSP. Em contraste, o SNP rs8099917 GG alelo foi associada com HAM/TSP, quando comprado aos indivíduos assintomáticos (OR = 6,25; IC95% = 1,22- 32,00). Conclusão: Pessoas com SNP rs8099917 genótipo GG podem apresentar uma resposta imune distinta contra a infecção pelo HTLV-1. Assim, parece razoável sugerir que uma pesquisa de polimorfismos IL28BSNP rs8099917 deve ser realizada em todos os indivíduos HTLV-1, a fim de monitorar o risco de desenvolvimento da doença. The polymorphism of IL28B was described as important in the pathogenesis of infections caused by some viruses. The aim of this research was to evaluate whether IL28B gene polymorphisms (SNP rs8099917 and SNP rs12979860) were associated with HAM/TSP. Methods: The study included 188 patients of the Institute of Infectious Diseases \"Emilio Ribas\" of São Paulo, they formed three groups: 117 subjects infected with HTLV-1(49 asymptomatic and 68 with HAM TSP), 47 chronic HCV monoinfected patients and 24 co-infected with HTLV-1 and HCV. Blood samples were collected and PBMC separated by density gradient centrifugation in Ficoll-Hypaque. DNA was extracted using a commercial kit, and the DNA was stored at -80 ° C for later analysis. Thereafter, the proviral load of individuals with HTLV-1 was quantified SNPs rs12979860 and rs8099917 in the region of IL28B were analyzed in all groups by PCR StepOnePlus system in real time. Results: A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphism SNP rs12979860 was not independently associated with HAM/TSP outcome. In contrast, the SNP rs8099917 allele GG was independently associated with HAM/TSP outcome (OR=6.25; IC95%=1.22- 32.00). Conclusion: Persons with SNP rs8099917 genotype GG may present a distinct immune response against HTLV-1 infection. So, it seems reasonable to suggest that a search for IL28B polymorphisms should be performed for all HTLV-1-infected subjects in order to monitor their risk for disease development; however, since this is the first description of this finding in the literature, we should first replicate this study with more HTLV-1-infected persons to strengthen the evidence already provided by our results.

Micronutrient deficiency is common in patients with HIV/AIDS, usually caused by mal-absorption and/or drug interactions. 25-hydroxyvitamin D is of fundamental importance for the homeostasis of musculoskeletal health. The current study aimed to evaluate the nutritional status of HIV-infected subjects in order to make their nutritional diagnoses, including their vitamin D blood levels, and to estimate their consumption of vitamin D. The study included 98 HIV-1-infected subjects, followed at University of São Paulo Medical School - HC-FMUSP. We performed a nutritional evaluation, along with the determination of patients’ serum 25-hydroxyvitamin D and calcium concentration, biochemical analyses, and an anthropometric assessment. In the medical interview a 24-hour food recall was used (R24) to estimate daily calorie intake, macronutrients, calcium, and vitamin D. A high level of vitamin D deficiency was observed in our patients: 83.4% of them had levels below 30 ng/ml; they also presented an increased risk of cardiovascular disease, along with a high consumption of dietary fat. Factors related to the virus itself and to the use of antiretroviral drugs may have contributed for the low vitamin D levels seen in our HIV-1-infected patients.

Background HTLV-1 infection may is present among HCV or HIVinfected subjects and is associated with higher risk for HAM/TSP and other inflammatory diseases. Lymphocytes from about half of HTLV-1-infected subjects spontaneously proliferate in vitro, and how this phenomenon relates to symptomatic disease outcome and viral burden is poorly understood. Objective: Evaluate T-cell proliferation in vitro and HTLV-1 proviral load (PVL) among co-infected subjects.

Micronutrient deficiency is common in patients with HIV/AIDS, usually caused by mal-absorption and/or drug interactions. 25-hydroxyvitamin D is of fundamental importance for the homeostasis of musculoskeletal health. The current study aimed to evaluate the nutritional status of HIV-infected subjects in order to make their nutritional diagnoses, including their vitamin D blood levels and to estimate their consumption of vitamin D. The study included 98 HIV-1-infected subjects, followed at University of São Paulo Medical School - HC-FMUSP. We performed a nutritional evaluation, along with the determination of patients’ serum 25-hydroxyvitamin D and calcium concentration, biochemical analyses and an anthropometric assessment. In the medical interview a 24-hour food recall was used (R24) to estimate daily calorie intake, macronutrients, calcium and vitamin D. A high level of vitamin D deficiency was observed in our patients: 83.4% of them had levels below 30 ng/ml; they also presented an increased risk of cardiovascular disease, along with a high consumption of dietary fat. Factors related to the virus itself and to the use of antiretroviral drugs may have contributed for the low vitamin D levels seen in our HIV-1-infected patients.