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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00028314
• Other study ID #: A5110
• Secondary ID: AACTG A5110ACTG
• Status: Completed
• Phase: N/A
• First received: December 20, 2001
• Last updated: July 26, 2013
• Start date: March 2002
• Est. completion date: March 2005

Study information

• Verified date: July 2013
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: March 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cachexia
• HIV Infections
• Lipodystrophy
• Wasting Disease

Intervention

Drug:
• Abacavir sulfate

• Atazanavir/Ritonavir

• Lopinavir/Ritonavir

• Nevirapine

Locations

Country	Name	City	State
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts
United States	Cook County Hosp. CORE Ctr.	Chicago	Illinois
United States	Northwestern University CRS	Chicago	Illinois
United States	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois
United States	Univ. of Cincinnati CRS	Cincinnati	Ohio
United States	MetroHealth CRS	Cleveland	Ohio
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	SSTAR, Family Healthcare Ctr.	Fall River	Massachusetts
United States	Univ. of Texas Medical Branch, ACTU	Galveston	Texas
United States	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii
United States	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	UCLA CARE Center CRS	Los Angeles	California
United States	University of Minnesota, ACTU	Minneapolis	Minnesota
United States	Vanderbilt Therapeutics CRS	Nashville	Tennessee
United States	Beth Israel Med. Ctr., ACTU	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania
United States	Rhode Island Hosp.	Providence	Rhode Island
United States	The Miriam Hosp. ACTG CRS	Providence	Rhode Island
United States	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri
United States	Washington U CRS	St. Louis	Missouri
United States	Harbor-UCLA Med. Ctr. CRS	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (6)

Calza L, Manfredi R, Chiodo F. Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother. 2004 Jan;53(1):10-4. Epub 2003 Nov 25. Review. — View Citation

Calza L, Manfredi R, Chiodo F. Hyperlipidaemia in patients with HIV-1 infection receiving highly active antiretroviral therapy: epidemiology, pathogenesis, clinical course and management. Int J Antimicrob Agents. 2003 Aug;22(2):89-99. Review. — View Citation

Carr A, Miller J, Law M, Cooper DA. A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS. 2000 Feb 18;14(3):F25-32. — View Citation

Mallal SA, John M, Moore CB, James IR, McKinnon EJ. Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection. AIDS. 2000 Jul 7;14(10):1309-16. — View Citation

McComsey G. Update on mitochondrial toxicity of antiretrovirals and its link to lipodystrophy. AIDS Rev. 2002 Jul-Sep;4(3):140-7. Review. — View Citation

Tebas P, Zhang J, Hafner R, Tashima K, Shevitz A, Yarasheski K, Berzins B, Owens S, Forand J, Evans S, Murphy R. Peripheral and visceral fat changes following a treatment switch to a non-thymidine analogue or a nucleoside-sparing regimen in HIV-infected s — View Citation

External Links

•   Click here for more information about abacavir sulfate
•   Click here for more information about atazanavir
•   Click here for more information about lopinavir/ritonavir
•   Click here for more information about nevirapine
•   Click here for more information about non-nucleoside reverse transcriptase inhibitors [NNRTIs]
•   Click here for more information about nucleoside reverse transcriptase inhibitors [NRTIs]
•   Haga clic aquí para ver información sobre este ensayo clínico en español.