HIV Infection, Mitochondrial Dysfunction
Conditions
Keywords
HIV, Lipoatrophy, mitochondrial dysfunction
Brief summary
The purposes of this study are to evaluate if switching an antiretroviral medication from efavirenz (EFV) to atazanavir/ ritonavir (ARV/r) will, in a 96-week period, change: 1. the amount of fat in HIV patients with lipoatrophy, 2. metabolic lab values such as your lipid (fat) profile, glucose (blood sugar), and insulin (a hormone that regulates glucose) in HIV patients with lipoatrophy.
Detailed description
Our study will evaluate the effects on peripheral fat of switching from EFV to ATV/r over 96 weeks in HIV+ patients with clinical lipoatrophy. From a virologic standpoint, EFV and ATV/r are medications which are recommended equally as preferred components of antiretroviral regimens in the December 2009 version of the Guidelines for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents.\[20\] The study subjects should be receiving a stable EFV-containing antiretroviral (ART) regimen for at least 48 weeks prior to study entry. Blood will be saved for further investigations if needed. Safety parameters will be regularly assessed throughout the study. In addition, a subcutaneous fat biopsy will be obtained to measure fat mtDNA, mtRNA, and fat apoptosis. These measurements would provide significant insight into the clinical changes which have been recently described.
Interventions
300 mg orally once daily with Ritonavir 100mg orally once daily for 96 weeks
DRUGEfavirenz
Maintain dosage - 600 mg orally QHS for 96 weeks
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Case Western Reserve University
Bristol-Myers Squibb
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. HIV infection 2. Age \> or = 18 years old. 3. Signed informed consent. 4. Clinical lipoatrophy of at least moderate severity and in at least two different areas of the following: face, arms, legs, or buttocks (as self reported by the patient and confirmed by the physician). 5. Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. 6. All subjects must not participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female subject/ male partner must use condoms (male or female) in addition to one of the following forms of contraception while on study: either a spermicidal agent, diaphragm, cervical cap, IUD, or hormonal-based contraception. Prior to study enrollment, women of childbearing potential (WOCBP) must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. 7. Receiving EFV-containing antiretroviral regimen for at least the last 48 weeks prior to study entry. Backbone NRTI regimens can include tenofovir, abacavir, emtricitabine, and/ or lamivudine. Backbone NRTI regimens cannot include zidovudine, stavudine, or didanosine. Breaks in therapy for a maximum of 5 consecutive days will be allowed during these 48 weeks, including the period immediately preceding study entry. 8. Patient willing and able to stop aspirin/ NSAIDS for 7 days before study entry and the scheduled skin biopsy procedures. 9. HIV-1 RNA \< 400 copies/mL for at least 90 days prior to study entry. 10. Laboratory values obtained within 60 days prior to study entry: 1. Absolute neutrophil count (ANC) ≥ 500 / mm3 2. Hemoglobin ≥ 9.0 g/dL 3. Platelet count ≥ 75,000/ mm3 4. Creatinine clearance \> 50 mL / min 5. PT/PTT \< 1.2 ULN
Exclusion criteria
1. Receipt of AZT, d4T, ddI, or ddC at study entry or within 24 weeks of entry 2. Life expectancy \< 12 months 3. Women who are pregnant or breastfeeding 4. WOCBP unwilling to use contraception WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period 5. Women with a positive pregnancy test. 6. Sexually active fertile men not using effective birth control if their partners are WOCBP. 7. Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in DEXA-measured Limb Fat Between the EFV and ATV/r Arms | 48 weeks | To examine the effect of switching from EFV- to ATV/r on limb fat in HIV-1 infected patients with established lipoatrophy, the primary objective of this trial will be to compare changes over 48 weeks in DEXA-measured limb fat between the EFV arm and ATV/r. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compare Changes in CD4, HIV-1 RNA Levels and Adverse Events in Two Arms | 96 weeks | To examine the effect of switching from EFV to ATV/r on safety in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in CD4 cell count, HIV-1 RNA levels, and adverse events between the EFV arm and the ATV/r arm |
| Compare Changes in Fat mtDNA, mtRNA and Fat Apoptosis Between the Two Arms | 96 weeks | To examine the effect of switching from EFV to ATV/r on fat mtDNA, mtRNA, and fat apoptosis in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in fat mtDNA, mt RNA levels and fat apoptosis between the EFV arm and ARV/r arm. |
| Comparing Fasting Lipid Levels Between the Two Arms | 96 weeks | To examine the effect of switching from EFV to ATV/r on lipids in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in fasting lipid levels between the EFV arm and ATV/r arm. |
| Compare Changes for DEXA-measured Limb Fat Between EFV and ATV/r Arms | 96 weeks | To examine the effect of switching from EFV- to ATV/r on limb fat in HIV-1 infected patients with established lipoatrophy, a secondary objective of this trial will be to compare changes over 96 weeks in DEXA-measured limb fat between the EFV arm and ARV/r. |
| Compare Changes in Levels of Hs-CRP Between the Two Arms | 96 weeks | To examine the effect of switching from EFV to ATV/r on highly sensitive C-reactive protein (hs-CRP) in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in hs (highly sensitive) - CRP levels between the EFV arm and the ATV/r arm. |
| Correlate the Changes in DEXA-measured Fat Limb With Fat mtDNA, mtRNA and Fat Apoptosis | 96 weeks | A secondary objective of this trial will be to correlate the changes in DEXA-measured limb fat with those of fat mtDNA, mtRNA levels and fat apoptosis |
| Comparing Glucose Metabolism (Fasting Insulin, QUIKI and HOMA-IR) Between the Two Arms | 96 weeks | To examine the effect of switching from EFV to ATV/r on glucose metabolism in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in fasting insulin, QUIKI and HOMA-IR between the EFV arm and the ATV/r arm |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Efavirenz 600 mg Serving as the Control Arm - patients will maintain EFV-containing antiretroviral regimen
Efavirenz: Maintain dosage - 600 mg orally QHS for 96 weeks | 1 |
| Arm B - Atazanavir/Ritonavir Atazanavir 300 mg orally with Ritonavir 100 mg orally once daily for 96 wks
Atazanavir/ritonavir: 300 mg orally once daily with Ritonavir 100mg orally once daily for 96 weeks | 0 |
| Total | 1 |
Baseline characteristics
| Characteristic | Efavirenz 600 mg | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants |
| Region of Enrollment United States | 1 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Change in DEXA-measured Limb Fat Between the EFV and ATV/r Arms
To examine the effect of switching from EFV- to ATV/r on limb fat in HIV-1 infected patients with established lipoatrophy, the primary objective of this trial will be to compare changes over 48 weeks in DEXA-measured limb fat between the EFV arm and ATV/r.
Time frame: 48 weeks
Population: Data not collected for analysis due to low enrollment and participant discontinuation.
Secondary
Compare Changes for DEXA-measured Limb Fat Between EFV and ATV/r Arms
To examine the effect of switching from EFV- to ATV/r on limb fat in HIV-1 infected patients with established lipoatrophy, a secondary objective of this trial will be to compare changes over 96 weeks in DEXA-measured limb fat between the EFV arm and ARV/r.
Time frame: 96 weeks
Population: Data not collected for analysis due to low enrollment and participant discontinuation.
Secondary
Compare Changes in CD4, HIV-1 RNA Levels and Adverse Events in Two Arms
To examine the effect of switching from EFV to ATV/r on safety in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in CD4 cell count, HIV-1 RNA levels, and adverse events between the EFV arm and the ATV/r arm
Time frame: 96 weeks
Population: Data not collected for analysis due to low enrollment and participant discontinuation.
Secondary
Compare Changes in Fat mtDNA, mtRNA and Fat Apoptosis Between the Two Arms
To examine the effect of switching from EFV to ATV/r on fat mtDNA, mtRNA, and fat apoptosis in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in fat mtDNA, mt RNA levels and fat apoptosis between the EFV arm and ARV/r arm.
Time frame: 96 weeks
Population: Data not collected for analysis due to low enrollment and participant discontinuation.
Secondary
Compare Changes in Levels of Hs-CRP Between the Two Arms
To examine the effect of switching from EFV to ATV/r on highly sensitive C-reactive protein (hs-CRP) in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in hs (highly sensitive) - CRP levels between the EFV arm and the ATV/r arm.
Time frame: 96 weeks
Population: Data not collected for analysis due to low enrollment and participant discontinuation.
Secondary
Comparing Fasting Lipid Levels Between the Two Arms
To examine the effect of switching from EFV to ATV/r on lipids in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in fasting lipid levels between the EFV arm and ATV/r arm.
Time frame: 96 weeks
Population: Data not collected for analysis due to low enrollment and participant discontinuation.
Secondary
Comparing Glucose Metabolism (Fasting Insulin, QUIKI and HOMA-IR) Between the Two Arms
To examine the effect of switching from EFV to ATV/r on glucose metabolism in HIV-1 infected patients, a secondary objective of this trial will be to compare changes over 96 weeks in fasting insulin, QUIKI and HOMA-IR between the EFV arm and the ATV/r arm
Time frame: 96 weeks
Population: Data not collected for analysis due to low enrollment and participant discontinuation.
Secondary
Correlate the Changes in DEXA-measured Fat Limb With Fat mtDNA, mtRNA and Fat Apoptosis
A secondary objective of this trial will be to correlate the changes in DEXA-measured limb fat with those of fat mtDNA, mtRNA levels and fat apoptosis
Time frame: 96 weeks
Population: Data not collected for analysis due to low enrollment and participant discontinuation.