HIV and HIV/HCV-Infection, Disease Progression, Oxidative Stress and Antioxidants

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Co-infection with Hepatitis C (HCV) is becoming the main cause of death in HIV-infected patients in the United States. Among drug users the proportion of HIV/HCV co-infection is 50%-90%. HCV infection leads to liver fibrosis, cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Current treatments for HIV/HCV co- infection result in a sustained suppression of HCV-RNA and histological improvement in less than 50% of the patients. Thus, other approaches to reversing fibrosis are needed due to ineligibility for treatment of a large proportion of patients, lack of response of eligible patients to treatment (up to 71% of patients) and discontinuation of treatment due to adverse effects. Oxidative stress is involved in the pathogenesis of hepatic damage leading to fibrosis in hepatitis C and is accompanied by decreased plasma micronutrient antioxidants. While many studies confirm the presence of elevated oxidative stress in HIV and in HCV mono-infections, no data are available for HIV/HCV co-infection. Our preliminary data indicate elevated oxidative stress and decreased antioxidant status in HIV/HCV co-infection compared to HIV mono-infection, and increased oxidative stress with more advanced fibrosis. Studies of antioxidant supplementation indicated that supplementation reduced oxidative stress, diminished stellate cell activation, and suppressed fibrogenesis in HCV mono-infection. Due to the lack of data in HIV/HCV co-infection, observational studies are needed prior to embarking on clinical trials. We propose to follow a cohort of 266 participants, 133 HIV/HCV co-infected and 133 HIV mono-infected, for 4 years. The co-infected group will be eligible for the study if they have no signs or early stage of fibrosis at their initial liver biopsy at baseline, and they will be biopsied again within 4 years of the study, or as soon as clinically indicated. Clinical examination and medical history and laboratory results from chart abstraction will document HIV staging (CD4 and viral load) co-morbidities, ART and other treatments. Questionnaires on demographics, BMI, food intake, and use of micronutrient supplements will be obtained and treated as covariates. Age and ART will be restricted, and co-morbid conditions which are associated with oxidative stress, will be excluded before the baseline visit. Blood will be drawn for metabolic profiles, complete blood count, plasma antioxidant micronutrients (vitamins A and E, 1 and 2-carotenes, zinc and selenium), and oxidative stress (malondialdehyde [MDA], reduced glutathione [GSH], and oxidized glutathione [GSSG]). This observational study is proposed to determine the association of oxidative stress and antioxidant status with HIV/HCV co-infection and progression of liver disease to provide the basis for potential future adjuvant therapies to reduce oxidative stress and suppress or delay fibrogenesis in HIV/HCV co- infected patients.NARRATIVE: Co-infection with Hepatitis C (HCV) is becoming the main cause of death in HIV-infected patients in the United States. Among drug users the proportion of HIV/HCV co-infection is 50%-90%. Oxidative stress is involved in the pathogenesis of hepatic damage leading to fibrosis in hepatitis C and is accompanied by decreased plasma micronutrient antioxidants. This observational study is proposed to determine the association of oxidative stress and antioxidant status with HIV/HCV co-infection and progression of liver disease to provide the basis for potential future adjuvant therapies to reduce oxidative stress and suppress or delay fibrogenesis in HIV/HCV co-infected patients.