Could Cesarean Delivery Help Prevent Mother-to-Child Transmission of Human T-Lymphotropic Virus Type 1?

BACKGROUND: Mother-to-child transmission (MTCT) of human T-lymphotropic virus type 1 (HTLV-1) is an important route of transmission that can cause lifelong infection. There is high morbidity and mortality due to adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy (HAM), and other inflammatory disorders. These conditions develop in nearly 10% of people with HTLV-1 infection, with a higher risk if infection occurs early in life. Identification of risk factors can inform targeted measures to reduce HTLV-1 MTCT. This study aimed to investigate the potential of cesarean delivery to prevent HTLV-1 MTCT. METHODS: We performed a review of the cases of women and their offspring under regular follow-up at the HTLV-1 outpatient clinic at the Institute of Infectious Diseases Emilio Ribas. RESULTS: A total of 177 HTLV-1-infected women and 369 adult offspring were investigated. Overall, 15% of the children were positive for HTLV-1 and 85% were negative. Regarding vertical transmission, we found that a breastfeeding duration of >6 months was associated with MTCT. Moreover, maternal proviral load was not associated with transmission, but high educational level and cesarean delivery were identified as protective factors. CONCLUSIONS: HTLV-1 MTCT was associated with mother's age at delivery of >25 years, low educational level, prolonged breastfeeding, and vaginal delivery.

AIDS incidence and survival in a hospital-based cohort of HIV-positive patients from São Paulo, Brazil: The role of IFN-λ4 polymorphisms.

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.

Education level explains differences in stroke incidence among city districts in Joinville, Brazil: a three-year population-based study.

BACKGROUND: Current evidence suggests an inverse association between socioeconomic status and stroke incidence. Our aim was to measure the variation in incidence among different city districts (CD) and their association with socioeconomic variables. METHODS: We prospectively ascertained all possible stroke cases occurring in the city of Joinville during the period 2005-2007. We determined the incidence for each of the 38 CD, age-adjusted to the population of Joinville. By linear regression analysis, we correlated incidence data with mean years of education (MYE) and mean income per month (MIPM). RESULTS: Of the 1,734 stroke cases registered, 1,034 were first-ever strokes. In the study period, the crude incidence in Joinville was 69.5 per 100,000 (95% confidence interval, 65.3-73.9). The stroke incidence among CD ranged from 37.5 (22.2-64.6) to 151.0 per 100,000 (69.0-286.6). The stroke incidence was inversely correlated with years of education (r = -0.532; p < 0.001). MYE and MIPM were strongly related (R = 0.958), resulting in exclusion of MIPM by collinearity. CONCLUSIONS: Years of education can explain a wide incidence variation among CD. These results may be useful to guide the allocation of resources in primary prevention policies.

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

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.

Prevalence of Antiretroviral Drug Resistance Mutations in HIV Seropositive Patients from an Outpatient Clinic of a Large University Hospital from São Paulo, Brazil.

Drug resistance mutations (DRMs) can affect the success of the therapy and compromise new prevention strategies. Increasing rates of resistance to antiretroviral (ARV) drugs have been reported in some areas. This study evaluated the DRMs prevalence among patients at Hospital das Clínicas (São Paulo). Among treatment-naive patients, the prevalence of transmitted DRMs (Stanford Calibrated Population Resistance) was 8.4% (21/249), with 69% (75/109) of acquired resistance among treatment-experienced patients. Rates of transmitted DRM showed an increase (6.6% in 2002-2009 vs. 15.1% in 2010-2015, p = .05), from the first to the second decade, mainly due to mutations to the NNRTI (non-nucleoside reverse transcriptase inhibitor) class. Among treatment-experienced cases, a nonsignificant decrease overall, significant for the protease inhibitors (PIs) class, was documented. Subtype B predominated in both groups (78%), followed by subtype F, BF recombinants, and subtype C. Our results add to the growing evidence of an increase in transmitted DRM, document extensive DRM among experienced patients, and a decrease in resistance to PIs class that may reflect the increased use of boosted PIs and newer ARV classes in more recent years.

Memory impairment: an intermediate clinical syndrome symptom in HTLV-1-infected patients?

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.

Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load.

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<0.001), visual disorders (p = 0.001), oral conditions (p = 0.001), skin lesions (p<0.001), bladder disorders (p<0.001), and rheumatological symptoms (p = 0.001), were strongly associated to IS, except for disautonomy (p = 0.21). A multivariate analysis revealed that HTLV-1 proviral load, oral conditions, bladder disorders and rheumatological symptoms were independently associated with the IS. CONCLUSIONS: We found some early alterations in 42 patients (24%), particularly the presence of previously not acknowledged clinical and neurological symptoms, among subjects previously classified as "asymptomatic", who we reclassified as having an intermediate syndrome.

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil.

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 São Paulo, Brazil. Methods: Since inception up to September 2018, we admitted 727 HTLV-1-infected individuals, with a rate of 30-50 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 São 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 [1.96-12.91], p = 0.001) Cox regression models. Coinfection with HIV/HCV was an independent predictor of increased mortality (HR 15.08; 95% CI [5.50-41.32]; p < 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 São 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.

Low DNA HTLV-2 proviral load among women in São Paulo City.

BACKGROUND: HTLV-2 infections are almost always asymptomatic, and diseases associated with the infection are rarely reported. Little information is available on the relationship between HTLV-2 proviral load and gender or expression of disease, especially among patients with HIV-1 co-infection. METHODS: We studied 77 HTLV-2-infected subjects followed in our clinic for the last 9 years; 53 (69%) of them were co-infected with HIV-1. HTLV-2 DNA proviral load (PVL) was measured by real time PCR, a test with a sensitivity of 10 in 10(4) PBMCs. RESULTS: Six of 53HTLV-2/HIV-1 cases had a myelopathy (all of them had undetectable PVL of HTLV-2). Only 3 of 35 women (2 out of 3 co-infected with HIV) had a detectable PVL, whereas 10 of 42 men had a detectable PVL. Regardless of their HIV status women had significantly lower PVL than men (10 vs. 43 copies/10(4) PBMCs, p<0.05). CONCLUSIONS: We noticed the occurrence of myelopathy in HTLV-2/HIV-1 co-infected patients, with undetectable HTLV-2 viral load. There was a sex difference in viral load for HTLV-2, what may be the result in mode of transmission or acquisition of the virus.

Is it possible to control HIV infection in a middle-income country through a multidisciplinary approach?

Despite the difficulties to follow and retain patients for a long time in the public health service, special programs may bring about increased chances of survival and better quality of life, as well as higher rates of retention in care; this is also true for middle-income developing countries such as Brazil. Our relatively small outpatient service (~500 HIV-infected patients) may not mirror the reality encountered in other settings, including São Paulo city, but retention and high quality of care may improve rates of virologic success, even in poorer settings. Furthermore, prevention of depression or anxiety, with discussion in groups of patients with the presence of a therapist, regular HIV RNA viral and CD4 cells counts, genotyping tests pre-HAART, and vigilance for drug failure, may explain this successful experience. We should also take into consideration that our cohort consists mostly of asymptomatic at-entry patients referred by the Blood Bank of São Paulo, located at the same Hospital, implying that they had a better immunological status at start than the more usual HIV population. Besides that, the degree of adherence to treatment in our service, in general, is quite high and the patients have a higher mean educational level; over 90% of the patients a high school or college education . Such features make this cohort a very specific and differentiated sample. In order to extend our findings, we intend to conduct similar studies in other HIV treatment centers, enabling comparisons of populations with different profiles.

In vitro basal T-cell proliferation among asymptomatic Human T cell Leukemia Virus type 1 patients co-infected with hepatitis C and/or Human Immunodeficiency Virus type 1.

BACKGROUND: Infection with Human T cell Leukemia Virus type 1 can be associated with myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory diseases. Lymphocytes from about half of Human T cell Leukemia Virus type 1-infected subjects spontaneously proliferate in vitro, and how this phenomenon relates to symptomatic disease and viral burden is poorly understood. OBJECTIVE: To evaluate T-cell proliferation in vitro among patients co-infected with Human T cell Leukemia Virus type 1/Hepatitis C Virus/Human Immunodeficiency Virus type 1. MATERIAL AND METHODS: From 610 Human T cell Leukemia Virus-infected patients of the Human T cell Leukemia Virus outpatient clinic from Institute of Infectious Diseases "Emilio Ribas" in São Paulo, 273 agreed to participate: 72 had HAM/TSP (excluded from this analysis) and 201 were asymptomatic, a classification performed during a regular neurological appointment. We selected the subgroup made up only by the 201 asymptomatic subjects to avoid bias by the clinical status as a confounder effect, who had laboratory results of Human T cell Leukemia Virus type 1 proviral load and T-cell proliferation assay in our database. They were further grouped according to their serological status in four categories: 121 Human T cell Leukemia Virus type 1 asymptomatic mono-infected carriers; 32 Human T cell Leukemia Virus type 1/Hepatitis C Virus, 29 Human T cell Leukemia Virus type 1/Human Immunodeficiency Virus type 1, and 19 Human T cell Leukemia Virus type 1/Human Immunodeficiency Virus type 1/Hepatitis C Virus co-infected patients. Clinical data were obtained from medical records and interviews. DNA Human T cell Leukemia Virus type 1 proviral load (PVL) and T-cell proliferation (LPA) assay were performed for all samples. RESULTS: From a total of 273 subjects with Human T cell Leukemia Virus type 1, 80 presented co-infections: 29 had Human Immunodeficiency Virus type 1, 32 had Hepatitis C Virus, and 19 had Human Immunodeficiency Virus type 1 and Hepatitis C Virus. Comparing the groups based on their serological status, independently of being asymptomatic carriers, we observed a significant increase of PVL (p<0.001) and LPA (p=0.001). However, when groups were stratified according to their clinical and serological status, there was no significant increase in Human T cell Leukemia Virus type 1 PVL and LPA. CONCLUSION: No significant increase of basal T-cell proliferation among Human T cell Leukemia Virus type 1 co-infected was observed. This interaction may be implicated in liver damage, worsening the prognosis of co-infected patients or, on the contrary, inducing a higher spontaneous clearance of Hepatitis C Virus infection in Human T cell Leukemia Virus type 1 co-infected patients.

Risk factors associated with HTLV-1 vertical transmission in Brazil: longer breastfeeding, higher maternal proviral load and previous HTLV-1-infected offspring.

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.

Polymorphisms in HLA-C and KIR alleles are not associated with HAM/TSP risk in HTLV-1-infected subjects.

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.

Identification of novel consensus CD4 T-cell epitopes from clade B HIV-1 whole genome that are frequently recognized by HIV-1 infected patients.

OBJECTIVE: To identify promiscuous and potentially protective human CD4 T-cell epitopes in most conserved regions within the protein-coding genome of HIV-1 clade B consensus sequence. DESIGN: We used the TEPITOPE algorithm to screen the most conserved regions of the whole genome of the HIV-1 subtype B consensus sequence to identify promiscuous human CD4 T-cell epitopes in HIV-1. The actual promiscuity of HLA binding of the 18 selected peptides was assessed by binding assays to nine prevalent HLA-DR molecules. Synthetic peptides were tested with interferon-gamma ELISPOT assays on peripheral blood mononuclear cells (PBMC) from 38 HIV-1 infected patients and eight uninfected controls. RESULTS: Most peptides bound to multiple HLA-DR molecules. PBMC from 91% of chronically HIV-1 infected patients recognized at least one of the promiscuous peptides, while none of the healthy controls recognized peptides. All 18 peptides were recognized, and each peptide was recognized by at least 18% of patients; 44% of the patients recognized five or more peptides. This response was not associated to particular HLA-DR alleles. Similar responses were obtained in CD8 T-cell-depleted PBMC. CONCLUSION: In silico prediction of promiscuous epitopes led to the identification of naturally immunodominant CD4 T-cell epitopes recognized by PBMC from a significant proportion of a genetically heterogeneous patient population exposed to HIV-1. This combination of CD4 T-cell epitopes - 11 of them not described before - may have the potential for inclusion in a vaccine against HIV-1, allowing the immunization of genetically distinct populations.

Women infected with HIV type 1 Brazilian variant, subtype B (B'-GWGR motif) have slower progression to AIDS, compared with patients infected with subtype B (B-GPGR motif).

INTRODUCTION: The Brazilian variant of human immunodeficiency virus (HIV) type 1 (HIV-1) subtype B (serotype B'-GWGR) has a tryptophan replacing a proline in position 328 of the HIV-1 envelope, a feature that may induce a different HIV disease progression. We aimed to evaluate the role of the B subtypes of HIV-1 (serotypes B-GPGR and B'-GWGR) on HIV disease progression. METHODS: A total of 137 HIV-infected individuals who had been admitted to the hospital were tested with an anti-V3 serologic assay, using peptides representing 2 HIV-1 subtype B strains, MN and SF2, and 2 Brazilian variant B'-GWGR strains, BR1 and BR2. RESULTS: Of 137 serum samples tested with the anti-V3 serologic assay, 4 (3%) yielded indeterminate results, 74 (54%; from 25 women and 49 men) were found to be B-GPGR, and 59 (43%; from 20 women and 39 men) were found to be the B'-GWGR variant. In general, a longer interval from the first known positive HIV test result to an AIDS-defining event was observed in the B'-GWGR group than in the B-GPGR group (21 vs. 7 months). The CD4+ T cell counts were higher in the B'-GWGR group (median CD4+ T cell count, 65 vs. 31 cells/mm3; P=.01), and women infected with the B'-GWGR variant were less likely to die than were men infected with the same variant (P=.01). The median viral load in the B'-GWGR group was 3.395 copies/mL, compared with 39.350 copies/mL in the B-GPGR group (P=.01). CONCLUSIONS: Taken together, our results indicate that B'-GWGR-infected women may have more-favorable outcomes than B-GPGR-infected subjects.

Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections.

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.

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.

Discordance between body mass index and anthropometric measurements among HIV-1-infected patients on antiretroviral therapy and with lipoatrophy/lipohypertrophy syndrome.

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). CONCLUSIONS: Anthropometric measurements were useful in the confirmation of the prevalence of LLS. BMI alone does not appear to be a good parameter for assessing the nutritional status of HIV-infected patients on HAART and with LLS. Other anthropometric measurements are needed to evaluate patients with the lipoatrophy/lipohypertrophy syndrome.

High frequency of deficient consumption and low blood levels of 25-hydroxyvitamin D in HIV-1-infected adults from São Paulo city, Brazil.

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.