title: Efficacy of a nucleoside-sparing regimen of darunavir/ritonavir plus raltegravir in treatment-naive HIV-1-infected patients (ACTG A5262).
abstract: OBJECTIVE
  To explore darunavir/ritonavir (DRV/r) plus raltegravir (RAL) combination therapy in antiretroviral-naive patients.
  
  
  METHODS
  Phase IIb, single-arm, open-label, multicenter study.
  
  
  METHODS
  One hundred and twelve antiretroviral-naive, HIV-1-infected patients received DRV/r 800/100 mg once daily and RAL 400 mg twice daily. Primary endpoint was virologic failure by week 24. Virologic failure was defined as confirmed viral load of 1000 copies/ml or more at week 12, or an increase of more than 0.5 log(10) copies/ml in viral load from week 4 to 12, or a confirmed viral load of more than 50 copies/ml at or after week 24. Protease and integrase genes were sequenced in patients experiencing virologic failure.
  
  
  RESULTS
  Virologic failure rate was 16% [95% confidence interval (CI) 10-24] by week 24 and 26% (95% CI 19-36) by week 48 in an intent-to-treat analysis. Viral load at virologic failure was 51-200 copies/ml in 17/28 failures. Adjusting for age and sex, virologic failure was associated with baseline viral load of more than 100,000 copies/ml [hazard ratio 3.76, 95% CI (1.52-9.31), P = 0.004] and lower CD4 cell count [0.77 per 100 cells/μl increase (95% CI 0.61-0.98), P = 0.037]. When trough RAL concentrations were included as a time-varying covariate in the analysis, virologic failure remained associated with baseline viral load more than 100,000 copies/ml [hazard ratio = 4.67 (95% CI 1.93-11.25), P < 0.001], whereas RAL level below detection limit in plasma at one or more previous visits was associated with increased hazard [hazard ratio = 3.42 (95% CI 1.41-8.26), P = 0.006]. All five participants with integrase mutations during virologic failure had baseline viral load more than 100,000 copies/ml.
  
  
  CONCLUSIONS
  DRV/r plus RAL was effective and well tolerated in most patients, but virologic failure and integrase resistance were common, particularly in patients with baseline viral load more than 100,000 copies/ml.
authors.affiliation: Division of Infectious Diseases, Northwestern University, Chicago, Illinois 60611, USA. b-taiwo@northwestern.edu
authors.forename: Babafemi
authors.initials: B
authors.lastname: Taiwo
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gallien
authors.forename: Roy M
authors.initials: RM
authors.lastname: Matining
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kuritzkes
authors.forename: Cara C
authors.initials: CC
authors.lastname: Wilson
authors.forename: Baiba I
authors.initials: BI
authors.lastname: Berzins
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
authors.forename: Barbara
authors.initials: B
authors.lastname: Bastow
authors.forename: Peter S
authors.initials: PS
authors.lastname: Kim
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011760:Pyrrolidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects; D000068898:Raltegravir Potassium; D019438:Ritonavir / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult; D016903:Drug Monitoring
chemical_list: D019380:Anti-HIV Agents; D011760:Pyrrolidinones; D012367:RNA, Viral; D013449:Sulfonamides; D000068898:Raltegravir Potassium; D019438:Ritonavir; D000069454:Darunavir