HIV Infections, Lipodystrophy, Metabolic Diseases, Nutrition Disorders
Conditions
Keywords
Lipoatrophy, Mitochondria, Treatment Naive
Brief summary
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.
Detailed 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.
Interventions
None listed
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mitochondrial Function (mtDNA Levels) | 96 weeks | Mitochondrial gene expression: mtDNA levels are used to quantify this outcome measure. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred from 6/2005 to 11/2008. Participants were recruited from 3 HIV clinics in Cleveland, with the majority from the clinic at University Hospitals Case Medical Center.
Pre-assignment details
Participants had to be HIV+ and naive to ARVs.
Participants by arm
| Arm | Count |
|---|---|
| ARV Naive ARV naive | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | ARV Naive |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 33.88 years STANDARD_DEVIATION 8.48 |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 18 |
| serious Total, serious adverse events | 2 / 18 |
Outcome results
Primary
Mitochondrial Function (mtDNA Levels)
Mitochondrial gene expression: mtDNA levels are used to quantify this outcome measure.
Time frame: 96 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ARV Naive | Mitochondrial Function (mtDNA Levels) | 1372 copies per cell |