Lipodystrophy associated with HIV infection is very frequent. It affects at least 50% of HIV-1-infected adults receiving antiretroviral therapy (ART) and can be stigmatizing leading to suboptimal adherence to antiretroviral treatment and subsequent clinical and virologic failure. The pathogenesis of this complication of HIV and its treatment is not completely understood. Clinical evidence suggests that specific nucleoside analogue reverse transcriptase inhibitors (particularly d4T and AZT) are associated with peripheral adipose tissue wasting, which may result from mitochondria! toxicity. Mitochondrial toxicity might be also be a contributor to other metabolic complications seen in patients treated for HIV. There has been considerable interest in using mitochondrial DNA measurements in PBMCs as predictors of nucleoside associated toxicity. So far reports have been conflicting because the studies have been underpowered and they lack of longitudinal objective assessments of body composition and other metabolic parameters. The goals of this proposal are: 1. To evaluate longitudinally the peripheral blood mononuclear cell (PBMC) mitochondrial DNA copy number across PBMC specimens obtained in several ACTG studies. 2. To evaluate relationships between longitudinal changes in PBMC mitochondrial DNA copy number and measures of insulin resistance, lipids and fat distribution in three ACTG studies. 3. To evaluate if the changes in mitochondrial DNA measured in PBMC during the first 16-24 weeks of therapy can be used as a predictors of which individuals will develop peripheral lipoatrophy. 4. Exploratory Aim. To evaluate relationships between longitudinal changes in PBMC mitochondrial RNA and RNA copy number and measures of insulin resistance, lipids and fat distribution in three ACTG studies. In order to do this we will use a NASBA based assay to measure the mitochondrial DNA and RNA content in PBMCs, and use 2000 specimens collected longitudinally in 3 large ACTG studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI063995-02
Application #
7060848
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Brobst, Susan W
Project Start
2005-05-01
Project End
2008-10-31
Budget Start
2006-05-01
Budget End
2008-10-31
Support Year
2
Fiscal Year
2006
Total Cost
$164,907
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104