Clinical trial NCT01194856: Switching From Efavirenz to Atazanavir/ Ritonavir in HIV-infected Subjects With Good Virologic Suppression
Official title: A Randomized Study to Evaluate the Effect of Switching From Efavirenz to Atazanavir/ Ritonavir on Lipoatrophy and Mitochondrial Dysfunction in HIV-infected Subjects With Good Virologic Suppression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: HIV Infection
Mitochondrial Dysfunction
Keywords: HIV
Lipoatrophy
mitochondrial dysfunction
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Case Western Reserve University
name: Bristol-Myers Squibb
First posted: 2010-09-03
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 Exclusion Criteria

   1. Prisoners or subjects who are involuntarily incarcerated.
   2. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
8. Clinically important illness within 14 days prior to study entry
9. Inability to communicate effectively with the study personnel.
10. Bleeding diathesis
11. Supplementation with recombinant growth hormone, growth hormone releasing factor, anabolic steroids, estrogen or testosterone, unless it is for replacement purposes.
12. Have no plans to alter any vitamin supplementation that subjects are receiving at study entry. This includes all vitamin supplementation, coenzyme Q, N acetyl cysteine, L-acetyl carnitine, and uridine.

Primary outcomes:
measure: Change in DEXA-measured Limb Fat Between the EFV and ATV/r Arms
timeFrame: 48 weeks
Secondary outcomes:
measure: Compare Changes for DEXA-measured Limb Fat Between EFV and ATV/r Arms
timeFrame: 96 weeks
measure: Compare Changes in CD4, HIV-1 RNA Levels and Adverse Events in Two Arms
timeFrame: 96 weeks
measure: Compare Changes in Fat mtDNA, mtRNA and Fat Apoptosis Between the Two Arms
timeFrame: 96 weeks
measure: Comparing Fasting Lipid Levels Between the Two Arms
timeFrame: 96 weeks
measure: Comparing Glucose Metabolism (Fasting Insulin, QUIKI and HOMA-IR) Between the Two Arms
timeFrame: 96 weeks
measure: Compare Changes in Levels of Hs-CRP Between the Two Arms
timeFrame: 96 weeks
measure: Correlate the Changes in DEXA-measured Fat Limb With Fat mtDNA, mtRNA and Fat Apoptosis
timeFrame: 96 weeks
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Marisa Tungsiripat, MD
role: PRINCIPAL_INVESTIGATOR
References: