HIV Infections
Conditions
Keywords
HIV, Lipodystrophy, Treatment Experienced
Brief summary
The metabolic and molecular basis of lipodystrophy syndrome in HIV-infected patients is not known. Whether besides protease inhibitors, other antiretroviral drugs, HIV infection and reduction in viral load contribute to the development of lipodystrophy syndrome is not clear. The project therefore has the following aims: 1) to characterize metabolic abnormalities and changes in body fat distribution, 2) to develop objective criteria for defining the syndrome and to ascertain prognostic indicators and 3) to elucidate the molecular basis of the lipodystrophy syndrome in HIV-infected patients.
Detailed description
A 2-year long prospective, randomized, double blind, placebo-controlled study in 200 asymptomatic HIV (+) patients to compare two equally effective antiretroviral regimens, one with and the other without a protease inhibiotor. We will study body fat distribution by anthropometry and magnetic resonance imaging and will measure insulin sensitivity (in a subset of patients), plasma lipoproteins, glucose tolerance and other metabolic variables. We will study expression of an array of adipocyte specific proteins/transcription factors involved in adipocyte differentiation, insulin action and lipoprotein metabolism in fat biopsy samples obtained before and after institution of therapy.
Interventions
DRUGNelfinavir
DRUGEfavirenz
Sponsors
Bristol-Myers Squibb
GlaxoSmithKline
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* HIV Positive * No previous antiviral therapy * 18 to 70 years of age
Exclusion criteria
* Patients with opportunistic infections or AIDS. * Active intravenous drug users. * Patients on corticosteroids, androgens, lipid-lowering drugs, anti-fungal medications, dehydroepiandrosterone, oxandrolone, megace. * Patients with diabetes mellitus. * Patients with moderate to heavy alcohol consumption ( greater than 15 drinks per week). * Pregnant or premenopausal women, unless surgically sterilized or highly unlikely to conceive (defined as women taking oral contraceptives, using barrier protection during intercourse or with a copper intrauterine device in place for \> 3 months without complaints and a negative serum or urine pregnancy test within 30 days of study entry). * Acute or chronic liver diseases; elevations of liver transaminases by more than two and one half times above the upper limits of normal ( SGOT \> 105 U/L, SGPT \> 120 U/L, ) or a total bilirubin of \> 1.5mg/dL. * Anemia (hematocrit \<32%). * Abnormal thyroid function tests. * Weight loss \>10% from baseline in the past year. * Recent (within the past year), history of suicide attempt.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Effect of Drug Regimens on Serum Triglycerides. | 12 and 24 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nelfinavir Randomized to receive Nelfinavir inclusive HAART | 28 |
| Efavirenz Randomized to receive Efavirenz inclusive HAART | 28 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12 Months | Abnormal Liver function tests | 0 | 5 |
| 12 Months | Drug allergy | 1 | 1 |
| 12 Months | High HIV viral load | 5 | 1 |
| 12 Months | Lipodystrophy | 2 | 0 |
| 12 Months | Withdrawal by Subject | 0 | 2 |
| 24 Months | Abnormal liver function tests | 1 | 5 |
| 24 Months | Lipodystrophy | 1 | 1 |
| 24 Months | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Nelfinavir | Efavirenz | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 28 Participants | 56 Participants |
| Body Mass Index | 25.2 kg/m2 STANDARD_DEVIATION 3.8 | 24.8 kg/m2 STANDARD_DEVIATION 5 | 24.9 kg/m2 STANDARD_DEVIATION 4.3 |
| CD4 count | 312 per cubic mm STANDARD_DEVIATION 210 | 301 per cubic mm STANDARD_DEVIATION 158 | 307 per cubic mm STANDARD_DEVIATION 185 |
| Fasting plasma glucose | 92.5 mg/dL STANDARD_DEVIATION 9 | 90.3 mg/dL STANDARD_DEVIATION 5.6 | 91.4 mg/dL STANDARD_DEVIATION 7.4 |
| HIV Viral load | 82000 copies per mL | 103000 copies per mL | 97900 copies per mL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 4 Participants | 13 Participants |
| Race (NIH/OMB) White | 14 Participants | 19 Participants | 33 Participants |
| Sex: Female, Male Female | 5 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 23 Participants | 24 Participants | 47 Participants |
| Triglycerides | 129 mg/dL STANDARD_DEVIATION 83.8 | 133.5 mg/dL STANDARD_DEVIATION 81.4 | 131.24 mg/dL STANDARD_DEVIATION 82 |
| Weight | 75.4 kgs STANDARD_DEVIATION 11 | 75 kgs STANDARD_DEVIATION 13.8 | 75.18 kgs STANDARD_DEVIATION 12.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 28 |
| other Total, other adverse events | 20 / 28 | 20 / 28 |
| serious Total, serious adverse events | 1 / 28 | 2 / 28 |
Outcome results
Primary
Effect of Drug Regimens on Serum Triglycerides.
Time frame: 12 and 24 months
Population: Some subjects dropped before 1 year and some dropped between 1-2 years.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nelfinavir (Viracept) | Effect of Drug Regimens on Serum Triglycerides. | At 12 months | 228.0 mg/dL | Standard Deviation 119 |
| Nelfinavir (Viracept) | Effect of Drug Regimens on Serum Triglycerides. | At 24 months | 293.4 mg/dL | Standard Deviation 350.6 |
| Efavirenz (Sustiva) | Effect of Drug Regimens on Serum Triglycerides. | At 12 months | 230.4 mg/dL | Standard Deviation 157.3 |
| Efavirenz (Sustiva) | Effect of Drug Regimens on Serum Triglycerides. | At 24 months | 290.0 mg/dL | Standard Deviation 276.1 |
p-value: 0.94Mixed Models Analysis