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Abacavir Substitution for Nucleoside Analogs in Patients With HIV Lipoatrophy
A Randomized Trial
Andrew Carr, MD;
Cassy Workman, MBBS;
Don E. Smith, MD;
Jennifer Hoy, MBBS;
Jeff Hudson, RN;
Nicholas Doong, MBBS, MPH;
Allison Martin, MSc;
Janaki Amin, MPH;
Judith Freund, MBBS;
Matthew Law, PhD;
David A. Cooper, MD, DSc;
for the Mitochondrial Toxicity (MITOX) Study Group
JAMA. 2002;288:207-215.
Context Peripheral lipoatrophy may complicate antiretroviral therapy of human
immunodeficiency virus (HIV) infection, often related to duration and type
of nucleoside analog therapy, and may have a mitochondrial pathogenesis. No
proven therapy exists for lipoatrophy, but abacavir is a nucleoside analog
that may be less toxic to mitochondria.
Objective To determine if substitution of stavudine or zidovudine with abacavir
improves HIV lipoatrophy without affecting control of HIV replication.
Design Randomized, open-label 24-week study.
Setting Seventeen hospital HIV outpatient clinics and primary care centers in
Australia and England, with randomization from June 2000 through January 2001.
Participants A total of 111 adults (109 men) with moderate or severe lipoatrophy
who were receiving stavudine (n = 85) or zidovudine (n = 26) and had stable
plasma HIV RNA levels below 400 copies/mL and no prior abacavir therapy.
Intervention Patients were randomly assigned to switch from stavudine or zidovudine
to abacavir, 300 mg twice per day, while continuing all other antiretroviral
therapy (n = 54) or to continue all antiretroviral therapy (n = 57).
Main Outcome Measures The primary end point was limb fat mass, measured by dual-energy x-ray
absorptiometry; key secondary end points were plasma HIV RNA levels, adverse
events, physician-assessed (via subjective measures) lipodystrophy severity,
total and central fat mass, and fasting metabolic (lipid, glycemic, and lactate)
levels.
Results There was a significant increase in limb fat in the abacavir group relative
to the stavudine/zidovudine group (0.39 vs 0.08 kg; mean difference, 0.31;
95% confidence interval [CI], 0.06-0.57 kg), as well as significant relative
increases in subcutaneous thigh (P = .01), arm (P<.001), and abdominal (P =
.001) fat areas on computed tomography. Switching had no significant effect
on secondary end points, including plasma HIV RNA (for unadjusted comparison
between groups at week 24, odds ratio, 1.38; 95% CI, 0.48-3.96). Change in
limb fat mass at week 24 did not correlate with change in subjectively determined
perceived lipoatrophy severity (r = -0.06; P = .53 by Spearman correlation). Hypersensitivity to abacavir
was seen in 5 patients (10%).
Conclusions In this sample of lipoatrophic HIV-infected adults, switching from stavudine
or zidovudine to abacavir for 24 weeks led to significant, albeit modest,
objectively measured increases in limb fat. Clinical lipoatrophy, as assessed
subjectively, did not resolve, however, and at the rate of increase observed
may take years to resolve with use of this strategy. Longer-term follow-up
is needed.
Author Affiliations: St Vincent's Hospital
(Drs Carr, Freund, and Cooper), AIDS Research Initiative (Dr Workman and Mr
Hudson), National Centre in HIV Epidemiology and Clinical Research, University
of New South Wales (Drs Smith, Law, and Cooper and Mss Martin and Amin), and
Burwood Road Medical Centre (Mr Hudson and Dr Doong), Sydney, Australia; and
Alfred Hospital and Monash University, Melbourne, Australia (Dr Hoy).
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