Brief Title
Effects of Treatment Changes on Fat Wasting in the Arms and Legs of HIV Patients
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
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.
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
Condition
HIV Infections
Intervention
Abacavir sulfate
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
150
Start Date
March 2002
Completion Date
March 2005
Eligibility 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
Gender
All
Ages
13 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Robert L Murphy, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00028314
Organization ID
A5110
Secondary IDs
AACTG A5110
Responsible Party
Sponsor
Study Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor
Robert L Murphy, MD, Study Chair, Northwestern University Medical Center
Verification Date
July 2013