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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA023405-05
Application #
8110023
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Khalsa, Jagjitsingh H
Project Start
2007-09-30
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$637,960
Indirect Cost
Name
Florida International University
Department
Nutrition
Type
Schools of Public Health
DUNS #
071298814
City
Miami
State
FL
Country
United States
Zip Code
33199
Martinez, Sabrina S; Campa, Adriana; Li, Yinghui et al. (2017) Low Plasma Zinc Is Associated with Higher Mitochondrial Oxidative Stress and Faster Liver Fibrosis Development in the Miami Adult Studies in HIV Cohort. J Nutr 147:556-562
Sneij, Alicia; Campa, Adriana; Martinez, Sabrina Sales et al. (2016) Lower Plasma Zinc Levels in Hyperglycemic People Living with HIV in the MASH cohort. J AIDS Clin Res 7:
Campa, Adriana; Martinez, Sabrina Sales; Sherman, Kenneth E et al. (2016) Cocaine Use and Liver Disease are Associated with All-Cause Mortality in the Miami Adult Studies in HIV (MASH) Cohort. J Drug Abuse 2:
Parsons, Mary; Campa, Adriana; Lai, Shenghan et al. (2013) Effect of GSTM1-Polymorphism on Disease Progression and Oxidative Stress in HIV Infection: Modulation by HIV/HCV Co-Infection and Alcohol Consumption. J AIDS Clin Res 4:
Shin, Dong-Ho; Martinez, Sabrina S; Parsons, Mary et al. (2012) Relationship of Oxidative Stress with HIV Disease Progression in HIV/HCV Co-infected and HIV Mono-infected Adults in Miami. Int J Biosci Biochem Bioinforma 2:217-223
Baum, M K; Sales, S; Jayaweera, D T et al. (2011) Coinfection with hepatitis C virus, oxidative stress and antioxidant status in HIV-positive drug users in Miami. HIV Med 12:78-86