The goals of this study are to find out if fat wasting and weight loss in the arms and legs of HIV patients taking highly active antiretroviral therapy (HAART) are caused by nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and if wasting can be reversed if the NRTI is stopped and replaced with other anti-HIV drugs.

Condition	Treatment or Intervention
HIV Infections Lipodystrophy Wasting Disease	Drug: Abacavir sulfate  Drug: Atazanavir/Ritonavir  Drug: Lopinavir/Ritonavir  Drug: Nevirapine

Further Study Details: 

Expected Total Enrollment:  150

Recent studies suggest body shape changes, fat redistribution, and fat lipoatrophy may be related to the NRTI component of patients' HAART and not to the protease inhibitor (PI) component. The hypothesis of this study is that thymidine analogues such as stavudine (d4T) and zidovudine (ZDV) cause lipoatrophy more so than non-thymidine analogues and that removal of thymidine analogues from HAART in patients with defined lipoatrophy will reverse this process.

In Step 1, patients will undergo axial mid-thigh and abdomen computer tomography (CT) scans. If the CT scans are readable, patients are restrictively and randomly assigned to 1 of 2 treatment arms in Step 2. Patients in Arm A-1 will replace the thymidine analogue component (stavudine [d4T] or zidovudine [ZDV]) of their HAART with abacavir (ABC). Patients in Arm B-1 will discontinue their current HAART and will receive a PI and a nonnucleoside reverse transcriptase inhibitor (NNRTI), either lopinavir/ritonavir (LPV/r) and nevirapine (NVP) or atazanavir, ritonavir, and NVP. Patients currently on efavirenz (EFV) not provided by the study may choose to continue with EFV instead of switching to NVP. Comparisons will be made to the baseline values of subcutaneous fat measured by mid-thigh and abdominal CT. Patients in Arms A-1 and B-1 remain on study for a total of 48 weeks and do not advance to Step 3.

Two additional groups (Arms A-2 and B-2) made no changes to HAART for 28 weeks to evaluate the natural history of change in lipoatrophy over time; accrual into these groups and into Step 3 has been discontinued. At Week 28, patients in Arms A-2 and B-2 were registered to Step 3 and switched from HAART to a designated new treatment. Arm A-2 patients will replace d4T or ZDV with ABC for 48 weeks. Arm B-2 patients replace their HAART with LPV/r plus NVP for 48 weeks. If patients in Arms A-2 and B-2 have not completed the 28-week delay and have not switched regimens, they will enter Step 4 and be reregistered into Arms A-1 and B-1, respectively, remaining on their treatment assignment for 48 weeks. If patients in Arms A-2 and B-2 have already switched regimens, then they will continue on their new regimens until Week 76.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Note: accrual into Arms A-2 and B-2 of this study has been discontinued.

Inclusion Criteria for Step 1

• HIV infected
• Experiencing a loss of fat since starting anti-HIV therapy, especially in the arms and legs
• Receiving anti-HIV therapy of 3 or more drugs, including either stavudine or zidovudine, for 24 weeks or more prior to study screening
• Viral load less than 500 copies/ml at study screening and within 60 days prior to study entry
• CD4 count of 100 or more cells/mm3 obtained within 60 days prior to study entry
• Approved methods of contraception
• Written informed consent

Exclusion Criteria for Step 1

• Currently receiving abacavir sulfate or have received abacavir sulfate in the past AND any or all of the following: unable to tolerate lopinavir/ritonavir (LPV/r) or nevirapine (NVP); failed anti-HIV treatment containing LPV/r, any other 2 PIs, or any other NNRTI; taking lamivudine (3TC) or tenofovir disoproxil fumarate (TDF) for hepatitis B virus infection and need to remain on a 3TC- or TDF-containing regimen; or have a low chance of response to LPV/r plus NVP
• Cancer treatment 6 months prior to study entry
• Initiated oral drugs to lower blood sugar level 24 weeks prior to study entry. Patients who have taken oral drugs to lower their blood sugar levels for 24 weeks or more prior to study entry are eligible.
• Began therapy with male sex hormones 24 weeks prior to study entry. Patients who have had continuous, stable therapy with male sex hormones for 24 weeks or more prior to study entry are eligible.
• Certain medications within 14 days prior to study entry
• Serious illness within 14 days prior to study entry
• Hepatitis within 60 days prior to study entry
• Thyroid problems
• Drug or alcohol use which, in the opinion of the investigator, would interfere with the study
• Currently using experimental agents except when approved by the study
• Pregnant or breastfeeding

California
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States
      Harbor General / UCLA, Torrance,  California,  90502-2052,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
Hawaii
      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
      The CORE Ctr, Chicago,  Illinois,  60612,  United States
Massachusetts
      Beth Israel Deaconess - West Campus, Boston,  Massachusetts,  02215,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455-0392,  United States
Missouri
      Washington Univ School of Medicine, St. Louis,  Missouri,  63108,  United States
      Washington Univ / St Louis Connect Care, Saint Louis,  Missouri,  63108,  United States
New York
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
Ohio
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
      MetroHealth Med Ctr, Cleveland,  Ohio,  44109-1998,  United States
      University of Cincinnati, Cincinnati,  Ohio,  45267-0405,  United States
Pennsylvania
      Univ of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
Rhode Island
      Miriam Hosp / Family Healthcare Ctr at SSTAR, Providence,  Rhode Island,  02906,  United States
      Miriam Hosp / Brown Univ, Providence,  Rhode Island,  02906,  United States
      Brown Univ / Miriam Hosp, Providence,  Rhode Island,  02906,  United States
Tennessee
      Comprehensive Care Clinic, Nashville,  Tennessee,  37203,  United States
Texas
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States

Study chairs or principal investigators

Robert L Murphy, MD,  Study Chair,  Northwestern University Medical Center   
Pablo Tebas, MD,  Study Chair,  University of Pennsylvania, Adult Clinical Trials Unit   

Study ID Numbers:  ACTG A5110; AACTG A5110
Record last reviewed:  December 2004
Last Updated:  April 7, 2005
Record first received:  December 20, 2001
ClinicalTrials.gov Identifier:  NCT00028314
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08