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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00028314
First received: December 20, 2001
Last updated: July 26, 2013
Last verified: July 2013
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 150
Study Start Date: March 2002
Study Completion Date: March 2005
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00028314

  Show 25 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Robert L Murphy, MD Northwestern University Medical Center
Study Chair: Pablo Tebas, MD University of Pennsylvania, Adult Clinical Trials Unit
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00028314     History of Changes
Other Study ID Numbers: A5110, AACTG A5110, ACTG A5110
Study First Received: December 20, 2001
Last Updated: July 26, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Abacavir
Nevirapine
Ritonavir
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
Acquired Immunodeficiency Syndrome
Lipodystrophy
Wasting Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Nutrition Disorders
Nevirapine
Ritonavir
Abacavir
Lopinavir
Atazanavir
Reverse Transcriptase Inhibitors
HIV Protease Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014