title: Abacavir substitution for nucleoside analogs in patients with HIV lipoatrophy: a randomized trial.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Randomized, open-label 24-week study.
  
  
  METHODS
  Seventeen hospital HIV outpatient clinics and primary care centers in Australia and England, with randomization from June 2000 through January 2001.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
authors.affiliation: HIV, Immunology and Infectious Diseases Clinical Services Unit, St Vincent's Hospital, Sydney, 2010 Australia. acarr@stvincents.com.au
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
authors.forename: Cassy
authors.initials: C
authors.lastname: Workman
authors.forename: Don E
authors.initials: DE
authors.lastname: Smith
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hoy
authors.forename: Jeff
authors.initials: J
authors.lastname: Hudson
authors.forename: Nicholas
authors.initials: N
authors.lastname: Doong
authors.forename: Allison
authors.initials: A
authors.lastname: Martin
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: Judith
authors.initials: J
authors.lastname: Freund
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.forename: David A
authors.initials: DA
authors.lastname: Cooper
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D001823:Body Composition; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D008055:Lipids / Q000097:blood; D008060:Lipodystrophy / Q000097:blood / Q000150:complications* / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D018119:Stavudine / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D008055:Lipids; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D015215:Zidovudine; D000099227:Abacavir