title: ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48-week results.
abstract: OBJECTIVE
  To evaluate the safety and antiviral activity of different dose levels of the HIV protease inhibitor ABT-378 combined with low-dose ritonavir, plus stavudine and lamivudine in antiretroviral-naive individuals.
  
  
  METHODS
  Prospective, randomized, double-blind, multicenter.
  
  
  METHODS
  Eligible patients with plasma HIV-1 RNA > 5000 copies/ml received ABT-378 200 or 400 mg with ritonavir 100 mg every 12 h; after 3 weeks stavudine 40 mg and lamivudine 150 mg every 12 h were added (group I, n = 32). A second group initiated treatment with ABT-378 400 mg and ritonavir 100 or 200 mg plus stavudine and lamivudine every 12 h (group II, n = 68).
  
  
  RESULTS
  Mean baseline HIV-1 RNA was 4.9 log10 copies/ml in both groups and CD4 cell count was 398 x 10(6)/l and 310 x 10(6)/l in Groups I and II respectively. In the intent-to-treat (ITT; missing value = failure) analysis at 48 weeks, HIV-1 RNA was < 400 copies/ml for 91% (< 50 copies/ml, 75%) and 82% (< 50 copies/ml, 79%) of patients in groups I and II respectively. Mean steady-state ABT-378 trough concentrations exceeded the wild-type HIV-1 EC50 (effective concentration to inhibit 50%) by 50-100-fold. The most common adverse events were abnormal stools, diarrhea and nausea. No patient discontinued before 48 weeks because of treatment-related toxicity or virologic rebound.
  
  
  CONCLUSIONS
  ABT-378 is a potent, well-tolerated protease inhibitor. The activity and durable suppression of HIV-1 observed in this study is probably attributable to the observed tolerability profile and the achievement of high ABT-378 plasma concentrations.
authors.affiliation: Department of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Murphy
authors.forename: S
authors.initials: S
authors.lastname: Brun
authors.forename: C
authors.initials: C
authors.lastname: Hicks
authors.forename: J J
authors.initials: JJ
authors.lastname: Eron
authors.forename: R
authors.initials: R
authors.lastname: Gulick
authors.forename: M
authors.initials: M
authors.lastname: King
authors.forename: A C
authors.initials: AC
authors.lastname: White
authors.forename: C
authors.initials: C
authors.lastname: Benson
authors.forename: M
authors.initials: M
authors.lastname: Thompson
authors.forename: H A
authors.initials: HA
authors.lastname: Kessler
authors.forename: S
authors.initials: S
authors.lastname: Hammer
authors.forename: R
authors.initials: R
authors.lastname: Bertz
authors.forename: A
authors.initials: A
authors.lastname: Hsu
authors.forename: A
authors.initials: A
authors.lastname: Japour
authors.forename: E
authors.initials: E
authors.lastname: Sun
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061466:Lopinavir; D008297:Male; D011744:Pyrimidinones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019438:Ritonavir / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018119:Stavudine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D019259:Lamivudine; D018119:Stavudine; D019438:Ritonavir