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

HIV Infections Clinical Trial

Official title:

Role of Mitochondria in the Development of HIV Atrophy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00119405
• Other study ID #: 1R01AI060484-01A2A
• Secondary ID: 1R01-AI060484-01
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 11, 2005
• Last updated: February 22, 2010
• Start date: April 2005
• Est. completion date: December 2010

Study information

• Verified date: December 2007
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Observational

Clinical Trial Summary

Nucleoside reverse transcriptase inhibitors (NRTIs) are a class of anti-HIV 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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Est. completion date: December 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• HIV Infections
• Lipodystrophy
• Metabolic Diseases
• Nutrition Disorders

Locations

Country	Name	City	State
United States	University Hospitals of Cleveland	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mitochondrial function		96 weeks	Yes
Primary	mtDNA		96 weeks	Yes
Secondary	fat apoptosis		96 weeks	Yes
Secondary	limb fat		96 weeks	Yes
Secondary	oxidative markers		96 weeks	Yes

External Links

•   Click here for more information about lipodystrophy
•   Click here for more information on starting anti-HIV medications