Switching From Efavirenz to Atazanavir/ Ritonavir in HIV-infected Subjects With Good Virologic Suppression
Condition: HIV Infection; Mitochondrial Dysfunction
MeSH terms: HIV Infections
Intervention: Atazanavir/ritonavir; Efavirenz
Intervention description: 300 mg orally once daily with Ritonavir 100mg orally once daily for 96 weeks; Maintain dosage - 600 mg orally QHS for 96 weeks
Intervention MeSH terms: Ritonavir; Atazanavir Sulfate; Efavirenz
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: HIV; Lipoatrophy; mitochondrial dysfunction

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.
    

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.