Effects of Treatment Changes on Fat Wasting in the Arms and Legs of HIV Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00028314
Recruitment Status : Completed
First Posted : December 21, 2001
Last Update Posted : July 29, 2013
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
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 or disease Intervention/treatment Phase
HIV Infections Lipodystrophy Wasting Disease Drug: Abacavir sulfate Drug: Atazanavir/Ritonavir Drug: Lopinavir/Ritonavir Drug: Nevirapine Not Applicable

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Restrictively Randomized, Open-Label, Controlled, Pilot Study of the Effect of a Thymidine Analogue Substitution or Change to a Nucleoside-Sparing Regimen on Peripheral Fat Wasting
Study Start Date : March 2002
Actual Study Completion Date : March 2005

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00028314

  Hide Study Locations
United States, California
Los Angeles, California, United States, 90095
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502-2052
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, Hawaii
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States
Indiana Univ. School of Medicine, Wishard Memorial
Indianapolis, Indiana, United States
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States
United States, Massachusetts
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
SSTAR, Family Healthcare Ctr.
Fall River, Massachusetts, United States
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455-0392
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
Saint Louis, Missouri, United States, 63108
Washington U CRS
St. Louis, Missouri, United States, 63108
United States, New York
Beth Israel Med. Ctr., ACTU
New York, New York, United States, 10003
New York, New York, United States, 10016
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267-0405
MetroHealth CRS
Cleveland, Ohio, United States, 44109-1998
The Ohio State University Medical Center
Columbus, Ohio, United States, 432101228
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
The Miriam Hosp. ACTG CRS
Providence, Rhode Island, United States, 02906
Rhode Island Hosp.
Providence, Rhode Island, United States
United States, Tennessee
Vanderbilt Therapeutics CRS
Nashville, Tennessee, United States, 37203
United States, Texas
Univ. of Texas Medical Branch, ACTU
Galveston, Texas, United States, 775550435
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Robert L Murphy, MD Northwestern University Medical Center
Study Chair: Pablo Tebas, MD University of Pennsylvania, Adult Clinical Trials Unit

Publications of Results:
Other Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00028314     History of Changes
Other Study ID Numbers: A5110
ACTG A5110
First Posted: December 21, 2001    Key Record Dates
Last Update Posted: July 29, 2013
Last Verified: July 2013

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
RNA, Viral
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
HIV Wasting Syndrome
ABT 378
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Wasting Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Weight Loss
Body Weight Changes
Body Weight
Signs and Symptoms
Nutrition Disorders
Atazanavir Sulfate
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors