title: Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naive patients: 4 year follow-up study.
abstract: OBJECTIVE
  Combination antiretroviral therapy with lopinavir/ritonavir (LPV/r) has been highly effective in clinical trials. Results of long-term therapy with LPV/r-based regimens have not been previously reported. This study describes the 4-year (204-week) safety and antiretroviral activity of LPV/r-based treatment in antiretroviral-naive individuals.
  
  
  METHODS
  Long-term, open-label follow-up of a phase II, prospective, randomized, multicenter trial.
  
  
  METHODS
  A group of 100 antiretroviral-naive HIV-infected patients were randomized to one of three blinded doses of LPV/r [200/100 mg (n = 16), 400/100 mg (n = 51), or 400/200 mg (n = 33)] with stavudine 40 mg and lamivudine 150 mg every 12 hours. After 48 weeks, LPV/r was dosed open-label at 400/100 mg every 12 hours with stavudine and lamivudine.
  
  
  RESULTS
  : Mean baseline plasma HIV-1 RNA and CD4 cell count were 4.9 log10 copies/ml and 338 x 10 cells/l, respectively. At week 204, 72 patients remained on study, 70 of whom had HIV-1 RNA < 50 copies/ml (70% by intent-to-treat analysis). Twenty-eight patients discontinued therapy prior to week 204 because of adverse events (n = 10), lost to follow-up (n = 9), or other reasons (n = 9). Of 15 patients who met protocol-defined criteria for virologic failure, seven remained on the study regimen and their HIV-1 RNA was re-suppressed to < 50 copies/ml at week 204. Genotypic analysis of rebound viral isolates was available from 10 patients, including all eight patients who discontinued the study prematurely. No isolate demonstrated primary or active site mutations in protease. The most common adverse events were gastrointestinal symptoms and lipid elevations.
  
  
  CONCLUSIONS
  LPV/r-based therapy provides durable antiretroviral response and is generally well tolerated through 204 weeks of therapy.
authors.affiliation: Duke University Medical Center, Durham, North Carolina, 27710, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Hicks
authors.forename: Martin S
authors.initials: MS
authors.lastname: King
authors.forename: Roy M
authors.initials: RM
authors.lastname: Gulick
authors.forename: A Clinton
authors.initials: AC
authors.lastname: White
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Harold A
authors.initials: HA
authors.lastname: Kessler
authors.forename: Constance
authors.initials: C
authors.lastname: Benson
authors.forename: Kathryn R
authors.initials: KR
authors.lastname: King
authors.forename: Robert L
authors.initials: RL
authors.lastname: Murphy
authors.forename: Scott C
authors.initials: SC
authors.lastname: Brun
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D011446:Prospective Studies; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage* / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019259:Lamivudine; D018119:Stavudine; D019438:Ritonavir