Tatiane Assone

IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in HTLV-1 carriers.

Background The polymorphisms of IL28B have been 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) are associated with HAM/TSP. Methods The study included 229 subjects, classified according to their neurological status in two groups: Group I (136 asymptomatic HTLV-1 carriers) and Group II (93 HAM/TSP patients). The proviral loads were quantified, and the rs8099917 and rs12979860 SNPs in the region of IL28B-gene were analyzed by StepOnePlus Real-time PCR System. Results A multivariate model analysis, including gender, age, and HTLV-1 DNA proviral load, showed that IL28B polymorphisms were independently associated with HAM/TSP outcome in rs12979860 genotype CT (OR = 2.03; IC95% = 0.96–4.27) and in rs8099917 genotype GG (OR = 7.61; IC95% = 1.82–31.72). Conclusion Subjects with SNP rs8099917 genotype GG and rs12979618 genotype CT 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 such 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.

Human papillomavirus infection in oral fluids of HIV-1-positive men:prevalence and risk factors

Human papillomavirus is one of the most common sexually transmitted diseases worldwide. The natural history of oral HPV infection is unclear, and its risk factors have not been explored. Immunocompromised individuals, as exemplified by HIV patients, are at high risk for HPV-related diseases. The mean of this study is to determine the prevalence ofHPV in the oral tract of HIV-1-positive male subjects and its association with risk factors. A total of 283 oral wash samples from HIV-1-positive men were tested. The oral fluid samples were used for DNA extraction and conventional PCR amplification; HPV genotyping was performed by hybridization. HPV genotyping revealed that nine samples (3.5%) were positive for HPV DNA; the major high-risk HPV types identified were 51 and 66. Worldwide studies have shown a variable prevalence of oral HPV. The diversity of genotypes and the high prevalence of multiple infections in HIV-infected subjects can be better explained by the effects of HIV-induced immunosuppression. The most important risk factors are unprotected sexual intercourse, but other factors for this infection have been described elsewhere including smoking, age and HIV-positive serostatus. In this study, smoking was the most important risk factor for acquiring oral HPV in HIV-1-infected subjects in Brazil.

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.

High risk of heterosexual transmission of human T-cell lymphotropic virus type 1 infection in Brazil

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.

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.

High specific immune response to a bivalent anti-HPV vaccine in HIV-1-infected men in São Paulo, Brazil

Introduction Infection with Human papillomavirus (HPV) has been reported as one of the most prevalent agent sexually transmitted diseases, but its true prevalence in men is not precisely known, mainly due to the near absence of symptoms. Moreover, few studies evaluating the post-vaccination immune response have been performed to date in men, hence the hypotheses tested in this study can be important to enable a better understanding of both the immunopathogenesis and the response to vaccination in HIV-infected patients, and to help in the elaboration of strategies of vaccination against HPV in the HIV-infected population. Objectives To analyze the specific response to antigens of HPV vaccine in HIV-infected men. Methods A total of 25 HIV-infected male patients who met the inclusion criteria during the data collection period were vaccinated; however, six (30%) had anti-HPV at baseline, and were not considered further in the analysis. Therefore, 19 HIV-infected individuals were included in the study, along with five healthy, HPV-seronegative controls. Results Patients infected with HIV-1 were subdivided into two groups, A and B, according to their T CD4 cells count at the time of vaccination, namely: Group A: CD4>500; Group B: CD4<500. The proportion of seroconversion after immunization with three doses of a bivalent anti-HPV vaccine was 92%. Conclusion HIV-infected patients as well as HIV negative controls responded to anti-HPV vaccination, regardless of their T CD4 cells count and HIV plasma viral load. These results demonstrate that anti-HPV immunization in HIV-infected males is effective and should be encouraged, thus helping to decrease the risk of infection, mortality and morbidity of diseases associated with HPV in men.

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.

Human T-cell lymphotropic virus type 1 (HTLV-1) infection among couples of a cohort followed up in São Paulo, Brazil

This study proposes to investigate the vertical and sexual HTLV-1 transmission rate in a coorte followed up in Sao Paulo, Brazil. The latter 173 HTLV-1-infected patients were selected until july 2014 (27.2% of 636 HTLV-1-infected individuals). Data were recorded using RedCap (Research Electronic Data Capture), transported to SPSS – Statistical Package for Social Sciences (v 20) and subjected to statistical analysis. To compare results between groups, one-way analysis of variance (one-way ANOVA test) was used. The vertical transmission rate found among 73 individuals born to HTLV-1-positive mothers was 6.8%. HTLV-1 concordant couples were compared to HTLV-1 discordant couples. Those coinfected with HIV were excluded from the sample. Among 91 individuals with stable partnership and without HIV, 49% did not know about the current partner serology: 39% of wives and 54.5% of husbands have not been tested. The horizontal transmission rate of HTLV-1 among those tested couples was 55.3%. Among men 68.2% of its wives were seropositive for HTLV-1, while among women 44.0% of its husbands were seropositive. HTLV-1 concordant couples (cases, n=6) were also compared to HTLV-1 discordant couples (controls, n=14), with respect to HTLV-1 proviral load. Those without HTLV-1 proviral load were excluded. In turn, the control group was subdivided into two subgroups: discordant couples with male index partner (n=5) and discordant couples with female index partner (n=9). Because of the impossibility of defining whether sexual transmission had occurred from man to woman or woman to man, for group 1 (concordant couples) we chose to use the average of the proviral loads of both partners in this group. Serodiscordant couples showed higher mean proviral loads (670 ±515 copias/104 peripheral blood mononuclear cell (PBMC)) compared with serodiscordant couples (282 ± 293 copias/104 PBMC) (p=0.045), probably associated with increased genital shedding of this virus and resulting increased risk of sexual transmission.

In vitro basal T-cell proliferation and HTLV-1 proviral load among HTLV-1 subjects co-infected with Hepatitis C and/or HIV-1

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.