title: Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment.
abstract: BACKGROUND
  Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects.
  
  
  METHODS
  An open-label, randomized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL) who were randomized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily (n = 52) or a regimen in which their PI was continued (n = 52) for 28 weeks. All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naive to abacavir and non-nucleoside reverse transcriptase inhibitors.
  
  
  RESULTS
  At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms, respectively. At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P < 0.001), LDL-cholesterol (-14 vs +5 mg/dL, P = 0.016), and triglycerides (-134 vs -36 mg/dL, P = 0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P = 0.583). A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades. At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count. Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments.
  
  
  CONCLUSIONS
  In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm3, substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment.
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas, USA. Philip.Keiser@utsouthwestern.edu
authors.forename: Philip H
authors.initials: PH
authors.lastname: Keiser
authors.forename: Michael G
authors.initials: MG
authors.lastname: Sension
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: Allan
authors.initials: A
authors.lastname: Rodriguez
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Olliffe
authors.forename: Vanessa C
authors.initials: VC
authors.lastname: Williams
authors.forename: John H
authors.initials: JH
authors.lastname: Wakeford
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Snidow
authors.forename: Anne D
authors.initials: AD
authors.lastname: Shachoy-Clark
authors.forename: Julie W
authors.initials: JW
authors.lastname: Fleming
authors.forename: Gary E
authors.initials: GE
authors.lastname: Pakes
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Hernandez
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D002784:Cholesterol / Q000097:blood / Q000145:classification; D015224:Dideoxynucleosides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced* / Q000517:prevention & control; D016018:Least-Squares Analysis; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood / Q000145:classification; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D002784:Cholesterol; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D008055:Lipids; D018894:Reverse Transcriptase Inhibitors; D014280:Triglycerides; D000099227:Abacavir