Nationwide Study of Drug Resistance Mutations in HIV-1 Infected Individuals under Antiretroviral Therapy in Brazil.

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008-2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.

Validation of CD4+ T-cell and viral load data from the HIV-Brazil Cohort Study using secondary system data.

BACKGROUND: The HIV-Brazil Cohort Study (HIV-BCS) is a research primarily based on data collection from medical records of people living with HIV/AIDS in Brazil. The aim of this study was to present the validating design and results for the laboratory biomarkers viral load and CD4+ T-cell count from the HIV-Brazil Cohort Study. METHODS: A total of 8007 patients who were started cART from 2003 to 2013 were considered eligible for this study. Total follow-up time was 32,397 years. The median duration of follow-up was 3.51 years (interquartile range - IQR 1.63-6.13 years; maximum 11.51 years). We used secondary data from the Brazilian Laboratory Tests Control System (SISCEL). Incidence of lab testing rates per 100 person years (100 py) were used to compare the number of laboratory tests carried out among cohort sites considering different databases for CD4+ T-cell counts and HIV viral load assessments. Descriptive statistics including 95% confidence interval, Pearson correlation coefficient, Bland-Altman agreement analysis and kappa coefficient agreement were applied for analysis. RESULTS: A total of 80,302 CD4+ T-cell counts and 79,997 HIV viral load assessments were observed in HIV-BCS versus 94,083 CD4+ T-cell counts and 84,810 viral loads from the Brazilian Laboratory Tests Control System. The general CD4+ T-cell HIV-BCS testing rate was 247 per 100 py versus 290 per 100 py and the viral load HIV-BCS testing rate was 246 per 100 py versus 261 per 100 py. The general correlation observed for the lowest quantitative CD4+ T-cell count before cART was 0.970 (p < 0.001) and for the log of the highest viral load before cART was 0.971 (p < 0.001). The general agreement coefficient for categorized CD4+ T-cell count was 0.932 (p < 0.001) and for viral load was 0.996 (p < 0.001). CONCLUSIONS: The current study confirms that biomarkers CD4+ T-cell count and viral load from the HIV-BCS have a high correlation and agreement with data from SISCEL, rendering both databases reliable and useful for epidemiological studies on HIV care in Brazil.

Factors associated with infant and adolescent mortality

Few studies have described factors associated with infant and adolescent mortality since birth. We report here mortality during a 20-year period in a birth cohort from Ribeirão Preto in order to identify birth variables that influenced mortality among infants and children between 10 and 19 years of age, the main causes of death, and the influence of social inequality at birth on death. Mothers were interviewed shortly after delivery. Social, biological and demographic information was collected, and mortality up to 19 years of age was investigated in registry systems. Of the 6748 liveborn singletons born in the municipality from 1978 to 1979, 343 died before or when 19 years of age were completed. Most of the cohort mortality (74.9 percent) occurred during the first year of life and 19.6 percent occurred from 10 to 19 years. Mortality was higher among boys. Preterm birth (hazard ratio, HR = 7.94) and low birth weight (HR = 10.15) were strongly associated with infant mortality. Other risk factors for infant mortality were: maternal age ³35 years (HR = 1.74), unskilled manual occupation of family head (HR = 2.47), and for adolescent mortality: unskilled manual occupation of family head (HR = 9.98) and male sex (HR = 6.58). "Perinatal conditions" were the main causes of deaths among infants and "external causes" among adolescents, especially boys. Socioeconomic factors at birth, represented by occupation, influenced adolescent mortality due to external causes, which was higher among boys (7:1). The influence of social inequality at birth on death, measured by occupation, was greater in adolescence than in infancy.