Effect of GSTM1-Polymorphism on Disease Progression and Oxidative Stress in HIV Infection: Modulation by HIV/HCV Co- Infection and Alcohol Consumption

Objective—To examine the effects of GSTM1 null-allele polymorphism on oxidative stress and disease progression in HIV infected and HIV/hepatitis C (HCV) co-infected adults. Methods—HIV-infected and HIV/HCV co-infected participants aged 40–60 years old with CD4 cell count \u3e350 cells/ μl, were recruited. GSTM1 genotype was determined by quantitative PCR. Oxidative stress (mitochondrial 8-oxo-2’-deoxyguanosine [8-oxo-dG], malondialdehyde [MDA], oxidized glutathione and Complexes I and IV), apoptosis and HIV disease (CD4 count and viral load) markers were measured. Gene copies were not quantified, thus the Hardy-Weinberg formula was not applicable. Results—Of the 129 HIV-infected participants, 58 were HIV/HCV co-infected. GSTM1 occurred in 66% (62/94) in those of African descent, and 33% (11/33) of the Caucasians. Those with GSTM1 coding for the functional antioxidant enzyme Glutathione S-transferase (GST), had higher CD4 cell count (β=3.48, p=0.034), lower HIV viral load (β=−0.536, p=0.018), and lower mitochondrial 8-oxo-dG (β=−0.28, p=0.03). ART reduced oxidative stress in the participants with the GSTM1 coding for the functional antioxidant enzyme. HIV/HCV co-infected participants with the GSTM1 coding for the functional antioxidant enzyme also had lower HIV viral load, lower 8- oxo-dG and lower rate of apoptosis, but also higher oxidized glutathione. Alcohol consumption was associated with lower HIV viral load but higher oxidized glutathione in those with the GSTM1 genotype coding for the functional antioxidant enzyme. Conclusion—The GSTM1 genotype coding for the functional antioxidant enzyme is associated with lower HIV disease severity, and with lower oxidative stress, compared to GSTM1 null-allele polymorphism. HCV co-infection and alcohol use may be associated with increased oxidative stress even in the presence of the GSTM1 coding for the functional antioxidant enzyme. The nullgene, on the contrary, appears to have a detrimental effect on immune function, viral load control, and antioxidant status, suggesting a potential benefit from antioxidants in HIV infected patients with the defective gene

Líneas de investigación del laboratorio de sistemas de información avanzados: dinámica de tecleo, computación afectiva, extracción de relaciones semánticas, blockchain & smart contracts

El Laboratorio de Sistemas de Información Avanzados (LSIA) de la Facultad de Ingeniería de la Universidad de Buenos Aires (UBA) cuenta con distintas líneas de investigación: Dinámica de Tecleo, Extracción de relaciones semánticas en español, Computación afectiva, Blockchain y Smart Contracts. En varias de estas líneas se han obtenido aportes relevantes al área mientras que otras están comenzando y mantienen objetivos prometedores.Eje: Innovación en Sistemas de Software.Red de Universidades con Carreras en Informátic

Líneas de investigación del laboratorio de sistemas de información avanzados: dinámica de tecleo, computación afectiva, extracción de relaciones semánticas, blockchain & smart contracts

El Laboratorio de Sistemas de Información Avanzados (LSIA) de la Facultad de Ingeniería de la Universidad de Buenos Aires (UBA) cuenta con distintas líneas de investigación: Dinámica de Tecleo, Extracción de relaciones semánticas en español, Computación afectiva, Blockchain y Smart Contracts. En varias de estas líneas se han obtenido aportes relevantes al área mientras que otras están comenzando y mantienen objetivos prometedores.Eje: Innovación en Sistemas de Software.Red de Universidades con Carreras en Informátic

Líneas de investigación del laboratorio de sistemas de información avanzados: dinámica de tecleo, computación afectiva, extracción de relaciones semánticas, blockchain & smart contracts

El Laboratorio de Sistemas de Información Avanzados (LSIA) de la Facultad de Ingeniería de la Universidad de Buenos Aires (UBA) cuenta con distintas líneas de investigación: Dinámica de Tecleo, Extracción de relaciones semánticas en español, Computación afectiva, Blockchain y Smart Contracts. En varias de estas líneas se han obtenido aportes relevantes al área mientras que otras están comenzando y mantienen objetivos prometedores.Eje: Innovación en Sistemas de Software.Red de Universidades con Carreras en Informátic

Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic, Antiretroviral-Naive, HIV-Infected Adults in Botswana

IMPORTANCE Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. OBJECTIVE To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), seleniumalone, or multivitamins with selenium vs placebo inafactorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. INTERVENTIONS Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. MAIN OUTCOMES AND MEASURES Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. RESULTS There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups. CONCLUSIONS AND RELEVANCE In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantl

Common variability in oestrogen-related genes and pancreatic ductal adenocarcinoma risk in women

The incidence of pancreatic ductal adenocarcinoma (PDAC) is different among males and females. This disparity cannot be fully explained by the difference in terms of exposure to known risk factors; therefore, the lower incidence in women could be attributed to sex-specific hormones. A two-phase association study was conducted in 12,387 female subjects (5436 PDAC cases and 6951 controls) to assess the effect on risk of developing PDAC of single nucleotide polymorphisms (SNPs) in 208 genes involved in oestrogen and pregnenolone biosynthesis and oestrogen-mediated signalling. In the discovery phase 14 polymorphisms showed a statistically significant association (P < 0.05). In the replication none of the findings were validated. In addition, a gene-based analysis was performed on the 208 selected genes. Four genes (NR5A2, MED1, NCOA2 and RUNX1) were associated with PDAC risk, but only NR5A2 showed an association (P = 4.08 × 10−5) below the Bonferroni-corrected threshold of statistical significance. In conclusion, despite differences in incidence between males and females, our study did not identify an effect of common polymorphisms in the oestrogen and pregnenolone pathways in relation to PDAC susceptibility. However, we validated the previously reported association between NR5A2 gene variants and PDAC risk

Alcohol Use Accelerates HIV Disease Progression

The effects of alcohol abuse on HIV disease progression have not been definitively established. A prospective, 30-month, longitudinal study of 231 HIV + adults included history of alcohol and illicit drug use, adherence to antiretroviral therapy (ART), CD4 + cell count, and HIV viral load every 6 months. Frequent alcohol users (two or more drinks daily) were 2.91 times (95% CI: 1.23–6.85, p  = 0.015) more likely to present a decline of CD4 to ≤200 cells/μl, independent of baseline CD4 + cell count and HIV viral load, antiretroviral use over time, time since HIV diagnosis, age, and gender. Frequent alcohol users who were not on ART also increased their risk for CD4 cell decline to ≤200 cells/mm 3 (HR = 7.76: 95% CI: 1.2–49.2, p  = 0.03). Combined frequent alcohol use with crack-cocaine showed a significant risk of CD4 + cell decline (HR = 3.57: 95% CI: 1.24–10.31, p  = 0.018). Frequent alcohol intake was associated with higher viral load over time (β = 0.259, p  = 0.038). This significance was maintained in those receiving ART (β = 0.384, p  = 0.0457), but not in those without ART. Frequent alcohol intake and the combination of frequent alcohol and crack-cocaine accelerate HIV disease progression. The effect of alcohol on CD4 + cell decline appears to be independent of ART, through a direct action on CD4 cells, although alcohol and substance abuse may lead to unmeasured behaviors that promote HIV disease progression. The effect of alcohol abuse on viral load, however, appears to be through reduced adherence to ART