Observational Study of Fat Loss in HIV Infected Adults Taking Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00119405
Recruitment Status : Completed
First Posted : July 13, 2005
Results First Posted : March 30, 2017
Last Update Posted : March 30, 2017
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

July 11, 2005
July 13, 2005
June 13, 2016
March 30, 2017
March 30, 2017
April 2005
November 2010   (Final data collection date for primary outcome measure)
Mitochondrial Function (mtDNA Levels) [ Time Frame: 96 weeks ]
Mitochondrial gene expression: mtDNA levels are used to quantify this outcome measure.
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Complete list of historical versions of study NCT00119405 on Archive Site
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Observational Study of Fat Loss in HIV Infected Adults Taking Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Role of Mitochondria in the Development of HIV Atrophy

Nucleoside reverse transcriptase inhibitors (NRTIs) are a class of anti-HIV (Human Immunodeficiency Virus) drug that can be an important part of an HIV treatment regimen. Because anti-HIV therapy may have negative side effects, there is a great need to carefully study HIV infected patients on such regimens. One negative side effect observed in many HIV infected patients is lipoatrophy, a condition that results in fat loss in the body. It is unclear if NRTIs also have a role in the development of mitochondrial toxicity, a condition that affects the body's ability to produce energy. The purpose of this study is to observe the effects of an NRTI-based, protease inhibitor (PI)-sparing drug regimen on fat loss in HIV infected, treatment-naive adults.

Study hypothesis: The initiation of NRTI-containing, PI-sparing therapy will inhibit mitochondrial DNA (mtDNA) synthesis and lead to a decrease in mtDNA content in adipose tissue, skeletal muscle and peripheral blood mononuclear cells (PBMCs), will cause deterioration in mitochondrial function, will increase fat apoptosis and oxidative damage biomarkers, and will lead to progressive decrease in body fat content.

NRTIs are a mainstay of HIV treatment regimens, often part of initial treatment regimens for newly diagnosed patients. Recent data suggest that NRTIs are responsible for lipoatrophy, a condition marked by progressive fat loss. Another negative side effect to antiretroviral (ARV) regimens is mitochondrial toxicity, which can damage the heart, nerves, muscles, kidneys, pancreas and liver, as well as affecting the body's ability to produce energy for important life processes. It has been hypothesized that lipoatrophy may be related to mitochondrial toxicity, but a causal relationship between the two has yet to be established. This study will examine HIV infected treatment-naive patients who are initiating their first ARV regimens. The regimens will contain 2 NRTI, one of which being zidovudine and a non-nucleoside reverse transcriptase inhibitor (NNRTI). The regimens will not contain any PIs.

Patients will participate in this study for 96 weeks. There will be 4 study visits at Weeks 12, 24, 48, and 96. Dual-energy x-ray absorptiometry (DEXA) scans and fat biopsies will occur at all visits. Additionally, blood collection for metabolic testing will occur at Week 12. ARVs will not be provided by this study.

Observational Model: Cohort
Time Perspective: Prospective
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Retention:   Samples With DNA
Fat and Blood for mitochindrial DNA and different nuclear genes that regulate fat and lipid metabolism
Non-Probability Sample
HIV positive adults starting their first antiretroviral regimen with either azidothymidine (AZT)-containing combination
  • HIV Infections
  • Lipodystrophy
  • Metabolic Diseases
  • Nutrition Disorders
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
November 2010
November 2010   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • HIV-1 infected
  • Treatment-naive
  • Plan to initiate first ARV regimen with 2 NRTIs and an NNRTI
  • Plan to include zidovudine as part of first ARV regimen

Exclusion Criteria:

  • Current use of steroids or growth hormone
  • Coagulopathies or other bleeding disorders
  • Pregnancy or breastfeeding
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
1R01AI060484-01A2 ( U.S. NIH Grant/Contract )
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National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
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Principal Investigator: Grace A. McComsey, MD University Hospitals Cleveland Medical Center
National Institute of Allergy and Infectious Diseases (NIAID)
December 2007