title: A randomized controlled trial of single-class maintenance therapy with abacavir/lamivudine/zidovudine after standard triple antiretroviral induction therapy: final 96-week results from the FREE study.
abstract: OBJECTIVE
  The aim of the study was to test the antiviral efficacy of a triple nucleoside reverse transcriptase inhibitor (NRTI) regimen, with potential beneficial metabolic effects, as maintenance therapy after induction with dual NRTIs and a boosted protease inhibitor (PI).
  
  
  METHODS
  An open-label, noninferiority study was carried out. Antiretroviral therapy (ART)-naïve patients with CD4 count ≤ 350 cells/μL and HIV-1 RNA >30000 copies/mL (n=207) were treated with zidovudine/lamivudine and lopinavir/ritonavir. After achieving HIV-1 RNA <50 copies/mL on two consecutive occasions between weeks 12 and 24 after baseline, 120 patients (baseline: median HIV-1 RNA 5.19 log10 copies/mL; median CD4 count 180 cells/μL) were randomized to receive abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) (n=61) or to continue the PI-based ART (n=59).
  
  
  RESULTS
  For the proportions of patients (intention-to-treat; missing=failure) with HIV-1 RNA <400 copies/mL (PI group, 66%; ABC/3TC/ZDV group, 71%) and <50 copies/mL (PI group, 63%; ABC/3TC/ZDV group, 62%) at 96 weeks, switching to ABC/3TC/ZDV was noninferior compared with continuing the PI regimen; the difference in failure rate (ABC/3TC/ZDV minus PI) was -4.4 percentage points [95% confidence interval (CI) -21.0 to +12.3 percentage points] and +0.4 percentage points (95% CI -16.9 to +17.7 percentage points), respectively. In the per protocol analysis, the difference in virological failure for HIV-1 RNA >400 copies/mL (0 of 39 patients in the PI group and two of 45 patients in the NRTI group) and for HIV-1 RNA >50 copies/mL (two of 39 and three of 45 patients, respectively) was +4.4 percentage points (95% CI -2.1 to +11.0 percentage points) and +1.5 percentage points (95% CI -8.6 to +11.7 percentage points), respectively, also showing noninferiority. Serum lipids significantly improved in the NRTI group, but not in the PI arm.
  
  
  CONCLUSIONS
  A single-class NRTI regimen after successful induction with standard ART had similar antiviral efficacy compared to continuation of a PI-based regimen at 96 weeks after baseline, with improved serum lipids.
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine and Infectious Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: H G
authors.initials: HG
authors.lastname: Sprenger
authors.forename: N
authors.initials: N
authors.lastname: Langebeek
authors.forename: P G H
authors.initials: PG
authors.lastname: Mulder
authors.forename: C H H
authors.initials: CH
authors.lastname: Ten Napel
authors.forename: R
authors.initials: R
authors.lastname: Vriesendorp
authors.forename: A I M
authors.initials: AI
authors.lastname: Hoepelman
authors.forename: J C
authors.initials: JC
authors.lastname: Legrand
authors.forename: P P
authors.initials: PP
authors.lastname: Koopmans
authors.forename: B
authors.initials: B
authors.lastname: Bravenboer
authors.forename: R W
authors.initials: RW
authors.lastname: Ten Kate
authors.forename: Php
authors.initials: P
authors.lastname: Groeneveld
authors.forename: Wfw
authors.initials: W
authors.lastname: Bierman
authors.forename: Ts
authors.initials: Ts
authors.lastname: van der Werf
authors.forename: Eh
authors.initials: E
authors.lastname: Gisolf
authors.forename: C
authors.initials: C
authors.lastname: Richter
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D001530:Belgium / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D002985:Clinical Protocols; D015224:Dideoxynucleosides / Q000008:administration & dosage*; D018450:Disease Progression; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D017320:HIV Protease Inhibitors; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008055:Lipids; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012367:RNA, Viral / Q000187:drug effects; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000008:administration & dosage*; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D008055:Lipids; D012367:RNA, Viral; D015215:Zidovudine; D000099227:Abacavir; C109078:lamivudine, zidovudine drug combination
keywords: abacavir/lamivudine/zidovudine; antiretroviral therapy; dyslipidaemia; induction maintenance; nucleoside reverse transcriptase inhibitors