Avaliação do perfi de mutações e resistência aos inibidores de transcriptase reversa e protease em variantes HIV presentes em pacientes coinfectados pleo VHC

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Oral health associated with quality of life of people living with HIV/AIDS in Brazil

Background: The epidemic of HIV/AIDS enters into its fourth decade and is still considered an important public health problem in developed and developing countries. The purpose is verify the oral health and other factors that influence the quality of life of people living with HIV/AIDS attending a public service reference in Brazil.Methods: The participants answered the questionnaire on socio-demographic conditions, issues related to HIV and daily habits. The quality of life was analyzed by the HIV/AIDS Targeted Quality of Life (HAT-QoL) instrument with 42 items divided into nine domains: General Activity, Sexual Activity, Confidentiality concerns, Health Concerns, Financial Concern, HIV Awareness, Satisfaction with Life Issues related to medication and Trust in the physician. The oral health data were collected by means of the DMFT index, use and need of dentures and the Community Periodontal Index, according to the criteria proposed by the World Health Organization, by a calibrated researcher. Bivariate and multiple linear regressions were performed.Results: Of the participants, 53.1% were women and had a mean age of 42 years, 53.1% had eight years or less of schooling and 20.3% were not employed. In analyzing the quality of life domain of the HAT-QoL, with a lower average there was: Financial concern (39.4), followed by Confidentiality concern (43.2), Sexual activities (55.2) and Health concerns (62. 88). There was an association between the variables: do not have link to employment (p < 0.001), is brown or black (p = 0.045), alcohol consumption (p = 0.041), did not make use of antiretroviral therapy (p = 0.006), high levels of viral load (p = 0.035) and need for dentures (p = 0.025), with the worse quality of life scores.Conclusion: Socioeconomic and inadequate health conditions had a negative impact on the quality of life of people with HIV/AIDS.

A perspective on the proposal for neurocognitive disorder criteria in DSM-5 as applied to HIV-associated neurocognitive disorders

HIV-associated neurocognitive disorders remain common in the current era of effective antiretroviral therapy. However, the severity at presentation of these disorders has been reduced, and the typical manifestations have changed. A revision of the American Academy of Neurology (AAN) criteria has been made on this basis, and a revision of the analogous criteria by the American Psychiatric Association will be forthcoming in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5. This article compares the relevant sets of diagnostic criteria that will be employed. It is concluded that a greater degree of integration of the revised, HIV-specific AAN criteria for HIV-associated neurocognitive disorders with the criteria proposed for the DSM-5 would prove advantageous for research, clinical, educational and administrative purposes.

Oral health status of people living with HIV/AIDS attending a specialized service in Brazil

Verify factors that influence the oral health status of people living with HIV/AIDS (PLWHA) in Brazil. The study was cross-sectional and includes 177 HIV-positive individuals, who answered questionnaire on the sociodemographic conditions, HIV aspects, habits, and satisfaction with the service. The oral health data were collected by means of the decayed, missing, and filled teeth (DMFT) index, use and need of dentures, and the Community Periodontal Index. Average number of the DMFT was 17.64. Most HIV-positive patients presented good periodontal status, 35.0% used dentures, 41.5% needed denture in the maxilla, and 62.0% in the mandible. In the multivariate analysis, older age and dissatisfaction with health care were associated with nonuse of dentures. The abandonment of the use of antiretroviral therapy increased the risk of PLWHA presenting more than three decayed teeth. Poor oral health of the PLWHA was mainly influenced by sociodemographic factors and use and satisfaction with service.

Human gammaherpesviruses viraemia in HIV infected patients

The Epstein-Barr virus (EBV) and Kaposi's sarcoma associated herpesvirus (KSHV) are consistently associated with lymphoproliferative diseases and cancers in humans, notably in patients with HIV. Our aim was to evaluate whether EBV and/or KSHV viral loads regularly assessed in peripheral blood mononuclear cells (PBMC) correlate with clinical or laboratorial parameters retrieved for patients living with HIV. This was a longitudinal study with a cohort of 157 HIV positive patients attending an academic HIV outpatient clinic in São Paulo State, Brazil. For each patient, up to four blood samples were collected over a 1 year clinical follow-up: on enrolment into the study, and after 4, 8 and 12 months. Total DNA was extracted from PBMC, and EBV and KSHV viral loads were assessed by real time quantitative PCR. Higher viral loads for EBV were significantly associated with high HIV viraemia, a greater number of circulating T CD8+ cells and lack of virological response to the antiretroviral treatment. KSHV viral load was undetectable in virtually all samples. EBV viral load in PBMC correlated with the number of circulating T CD8+ lymphocytes and the response to the antiretroviral therapy in HIV infected patients. In contrast, KSHV was undetectable in PBMC, presumably an effect of the antiretroviral treatment. Therefore, either KSHV infection in the population studied was absent or viral load in PBMC was beyond the analytical limit of the assay.

Anthropometric indicators predict metabolic syndrome diagnosis in maintenance hemodialysis patients

Obesity has been considered the key in metabolic syndrome (MetS) development, and fat accumulation may be responsible for the occurrence of metabolic abnormalities in hemodialysis patients. The use of gold-standard methods to evaluate obesity is limited, and anthropometric measures may be the simplest methods. However, no study has investigated the association between anthropometric indexes and MetS in these patients. Therefore, the aim was to determine which anthropometric indexes had the best association and prediction for MetS in patients undergoing hemodialysis. Cross-sectional study that included patients older than 18 years, undergoing hemodialysis for at least 3 months. Patients with liver disease and cancer or those receiving corticosteroids or antiretroviral therapy were excluded. Diagnostic criteria from Harmonizing Metabolic Syndrome were used for the diagnosis of MetS. Anthropometric indexes evaluated were body mass index (BMI); percent standard of triceps skinfold thickness and of middle arm muscle circumference; waist circumference (WC); sagittal abdominal diameter; neck circumference; waist-to-hip, waist-to-thigh, and waist-to-height ratios; sagittal index; conicity index; and body fat percentage. Ninety-eight patients were included, 54.1% male, and mean age was 57.8 ± 12.9 years. The prevalence of MetS was 74.5%. Individuals with MetS had increased accumulation of abdominal fat and general obesity. Waist-to-height ratio was the variable independently associated with MetS diagnosis (odds ratio, 1.21; 95% confidence interval, 1.09-1.34; P < .01) and that better predicts MetS, followed by WC and BMI (area under the curve of 0.840, 0.836, and 0.798, respectively, P < .01). Waist-to-height ratio was the best anthropometric predictor of MetS in maintenance hemodialysis patients.

Alterações mamográficas em mulheres que vivem com HIV-aids

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Marcadores de ativação imune, inflamação crônica e estresse oxidativo em pessoas que vivem com o HIV/Aids: a busca do melhor prognóstico

Pós-graduação em Doenças Tropicais - FMB

Genital infections of HIV-infected women assisted by a specialized service

The present study aimed at analyzing the persistence/recurrence of genital infections and its associated factors in HIV-infected women. Fifty-eight women treated for chlamydial infection, trichomoniasis, vulvovaginal candidiasis, and/or bacterial vaginosis (BV) and who had specimens collected for cure control up to one year after treatment were studied. Diagnoses were performed by the Gram staining method for cases of BV and candidiasis and by T. vaginalis culture and qualitative PCR for C. trachomatis. Antiretroviral therapy was used by 79.3% of patients, and 62.1% showed an undetectable HIV plasma load. The most frequent infection was BV with persistence/recurrence of 52.4%, which was associated with a longer time period between treatment and cure control (P = 0.0455), postmenopausal period (P = 0.0451), and having a steady partner (P = 0.007). Persistence/recurrence of vulvovaginal candidiasis was observed in 25%, trichomoniasis in 23.1%, and chlamydial infection in 10.5%. The letter was associated with inadequate treatment of the partner (P = 0.073) among patients with low T CD4 lymphocyte counts. The majority of women in the present study showed good HIV-infection control and a vulnerable sexual behavior, which stress the importance of maintaining gynecological followup.

Influência da infecção pelo HIV e do uso da terapia antirretroviral nas concentrações de selênio, selenometionina e proteção antioxidante

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência da infecção pelo HIV e do uso da terapia antirretroviral nas concentrações de selênio, selenometionina e proteção antioxidante

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Low-Cost Ultra-Wide Genotyping Using Roche/454 Pyrosequencing for Surveillance of HIV Drug Resistance

Background: Great efforts have been made to increase accessibility of HIV antiretroviral therapy (ART) in low and middle-income countries. The threat of wide-scale emergence of drug resistance could severely hamper ART scale-up efforts. Population-based surveillance of transmitted HIV drug resistance ensures the use of appropriate first-line regimens to maximize efficacy of ART programs where drug options are limited. However, traditional HIV genotyping is extremely expensive, providing a cost barrier to wide-scale and frequent HIV drug resistance surveillance. Methods/Results: We have developed a low-cost laboratory-scale next-generation sequencing-based genotyping method to monitor drug resistance. We designed primers specifically to amplify protease and reverse transcriptase from Brazilian HIV subtypes and developed a multiplexing scheme using multiplex identifier tags to minimize cost while providing more robust data than traditional genotyping techniques. Using this approach, we characterized drug resistance from plasma in 81 HIV infected individuals collected in Sao Paulo, Brazil. We describe the complexities of analyzing next-generation sequencing data and present a simplified open-source workflow to analyze drug resistance data. From this data, we identified drug resistance mutations in 20% of treatment naive individuals in our cohort, which is similar to frequencies identified using traditional genotyping in Brazilian patient samples. Conclusion: The developed ultra-wide sequencing approach described here allows multiplexing of at least 48 patient samples per sequencing run, 4 times more than the current genotyping method. This method is also 4-fold more sensitive (5% minimal detection frequency vs. 20%) at a cost 3-5 x less than the traditional Sanger-based genotyping method. Lastly, by using a benchtop next-generation sequencer (Roche/454 GS Junior), this approach can be more easily implemented in low-resource settings. This data provides proof-of-concept that next-generation HIV drug resistance genotyping is a feasible and low-cost alternative to current genotyping methods and may be particularly beneficial for in-country surveillance of transmitted drug resistance.

Lipid levels in the second year of life among HIV-infected and HIV-exposed uninfected Latin American children

Background: Dyslipidemia is observed among older children and adults with HIV. We examined nonfasting cholesterol and triglycerides in two groups of 12-23-month-old Latin American children - HIV-infected vs. HIV-exposed but uninfected (HEU). Methods: HIV-infected and HEU children in Latin America and Jamaica were enrolled in an observational cohort. Eligibility for this analysis required having cholesterol and triglyceride results available during the second year of life. Results: HIV-infected (n = 83) children were slightly older at the time of lipid testing than the HEU (n 681). Forty percent of the HIV-infected children were on protease inhibitor-based antiretroviral therapy (ART); 41% were not on ART. There was no statistically significant difference in mean cholesterol concentrations (mg/dl) by HIV status; however, the HIV-infected children had higher mean triglyceride concentrations. The prevalence of high cholesterol (>200 mg/dl) and high triglycerides (>110 mg/dl) was higher among the HIV-infected vs. HEU. Among the HIV-infected children, mean cholesterol and triglyceride concentrations varied by ART. Children receiving no ART had a significantly lower mean cholesterol concentration. Those receiving protease inhibitor-containing ART had a significantly higher mean triglyceride concentration compared to the other two antiretroviral regimen groups. Conclusion: A greater proportion of HIV-infected children at 12-23 months have hyperlipidemia when compared to HEU children, with the highest triglyceride concentrations observed among those receiving protease inhibitor-containing ART, and the lowest cholesterol levels among those not receiving ART. Implications of these findings will require continued follow-up of HIV-infected children who initiate therapy early in life. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Age-Related Expansion of Tim-3 Expressing T Cells in Vertically HIV-1 Infected Children

As perinatally HIV-1-infected children grow into adolescents and young adults, they are increasingly burdened with the long-term consequences of chronic HIV-1 infection, with long-term morbidity due to inadequate immunity. In progressive HIV-1 infection in horizontally infected adults, inflammation, T cell activation, and perturbed T cell differentiation lead to an "immune exhaustion'', with decline in T cell effector functions. T effector cells develop an increased expression of CD57 and loss of CD28, with an increase in co-inhibitory receptors such as PD-1 and Tim-3. Very little is known about HIV-1 induced T cell dysfunction in vertical infection. In two perinatally antiretroviral drug treated HIV-1-infected groups with median ages of 11.2 yr and 18.5 yr, matched for viral load, we found no difference in the proportion of senescent CD28(-)CD57(+)CD8(+) T cells between the groups. However, the frequency of Tim-3(+)CD8(+) and Tim-3(+)CD4(+) exhausted T cells, but not PD-1(+) T cells, was significantly increased in the adolescents with longer duration of infection compared to the children with shorter duration of HIV-1 infection. PD-1(+)CD8(+) T cells were directly associated with T cell immune activation in children. The frequency of Tim-3(+)CD8(+) T cells positively correlated with HIV-1 plasma viral load in the adolescents but not in the children. These data suggest that Tim-3 upregulation was driven by both HIV-1 viral replication and increased age, whereas PD-1 expression is associated with immune activation. These findings also suggest that the Tim-3 immune exhaustion phenotype rather than PD-1 or senescent cells plays an important role in age-related T cell dysfunction in perinatal HIV-1 infection. Targeting Tim-3 may serve as a novel therapeutic approach to improve immune control of virus replication and mitigate age related T cell exhaustion.

Quality of life among Brazilian women living with HIV/AIDS

The purpose of the present study was to assess quality of life (QoL) in Brazilian women living with HIV/AIDS, according to the World Health Organization Quality of Life HIV-BREF (WHOQoL-HIV-BREF) domains. A quantitative-based, cross-sectional, analytical study was carried out in healthcare centers specialized in assisting people living with HIV/AIDS, located in a municipality of the state of Sao Paulo, Brazil. One hundred and six women of age 18 years or more, users of the public healthcare system, participated in the study. Socio-demographic and clinical variables were collected using a specific questionnaire. Quality of life related variables were collected by means of the WHOQoL-HIV-BREF instrument. As per the QoL domains, study results show that the Spirituality domain reached a standardized mean score of 65.7, followed by the Physical (64.7), Psychological (60.6), Social Relationships (59.5), Independence (58.6), and Environment (54.5) domains. Results of the multiple regression analysis indicate that the women's employment or retirement, income greater than the minimum wage, and higher educational level were associated with a higher standardized mean score of QoL. However, recent HIV/AIDS diagnosis and exposure to antiretroviral agents for a period shorter than two years were negatively associated with QoL. It is critical that public policies favor an all-embracing social inclusion of these women, thus promoting better social conditions. Counseling, clinical follow-up immediately after the infection diagnosis, and initiation of antiretroviral treatment are crucial moments in the lives of these individuals.