Raltegravir Therapy for Women With HIV and Fat Accumulation
Condition: HIV Infections; Lipodystrophy
MeSH terms: Lipodystrophy
Intervention: raltegravir
Intervention description: raltegravir
Intervention MeSH terms: Raltegravir Potassium
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: lipodystrophy; fat; visceral fat; HIV; women; raltegravir; ART; anti HIV therapy; NNRTI; Protease inhibitor; integrase inhibitor; treatment experienced

Summary:

      Ritonavir-boosted protease inhibitor (PI) regimens have become a backbone for treatment of
      people with HIV. However, adverse drug effects, particularly lipodystrophy/lipoatrophy are
      closely associated with these regimens. Therefore, there is a need for a drug with comparable
      effectiveness to the ritonavir boosted PIs without the side effects of dyslipidemia, which
      has been associated with elevated cholesterol and cardiovascular disease

      Raltegravir is an HIV integrase inhibitor in phase III clinical development. To date there
      are no approved drugs that target the same stage of the HIV-1 lifecycle. However, data from
      studies indicate that raltegravir is generally safe and well tolerated and has strong
      antiretroviral activity when used in combination with licensed antiretroviral medications.

      This study aims to demonstrate that patients substituting raltegravir for a PI or NNRTI based
      antiretroviral regimen will be associated with a 10% reduction in body fat over 24 weeks.

      The study will consist of a total of 10 subject visits over a period of 48 weeks.
      Approximately 40 female patients will participate in this study (approximately 10 at UCLA).
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV-1 infection as documented by any licensed ELISA test kit and confirmed by Western
             blot at any time prior to study entry or plasma HIV-1 RNA > 2000 on two occasions,

          -  Female subjects 18 years or older

          -  Documented central fat accumulation (defined by waist circumference of > 94 cm or a
             waist to hip ratio of > 0.88).

          -  Documented HIV RNA <50 copies/mL at screening and <400 copies/mL in the past 6 months.

          -  Current antiretroviral therapy with two nucleoside analogues and either a
             non-nucleoside analogue (nevirapine, efavirenz or TMC125) or an approved protease
             inhibitor. Patients on NNRTI+PI at study entry will be excluded. Study participants do
             not need to be on their first regimen. No changes in ART in the 12 weeks prior to
             screening. The nucleoside backbone must include either tenofovir or abacavir and
             either lamivudine or emtricitabine. Fixed dose combinations with emtricitabine or
             abacavir are allowed.

          -  For females of reproductive potential (women who have not been post-menopausal for at
             least 24 consecutive months, i.e., who have had menses within the preceding 24 months,
             or women who have not undergone surgical sterilization, specifically hysterectomy, or
             bilateral oophorectomy and/or tubal ligation), will need a negative serum or urine
             pregnancy test within 48 hours prior to entry.

          -  Ability and willingness of subject to provide informed consent.

        Exclusion Criteria:

          -  Pregnancy: current or within the past 6 months or breast feeding

          -  Prior treatment history that would preclude the use of emtricitabine or abacavir as
             the nucleoside backbone during study treatment

          -  Current use of metformin or thiazolidinediones.

          -  Use of growth hormone or growth hormone releasing factor in the last 6 months before
             screening.

          -  Change or initiation of anti-hyperlipemic regimen within 3 months prior to
             randomization; Use of stable anti-hyperlipemic regimen during the study is allowed.

          -  Current use of androgen therapy.

          -  Intent to modify diet, exercise habits or to enroll in a weight loss intervention
             during the study period.

          -  Current or projected need to use rifampin, dilantin or phenobarbital during the
             48-week study period.

          -  Laboratory values at screening of

               -  ANC >500 cells/mm3

               -  Hemoglobin <10 gm/dl

               -  CrCl > 60 ml/min (estimated by Cockcroft-Gault equation)

               -  AST or ALT > 3 x ULN