title: Vicriviroc in combination therapy with an optimized regimen for treatment-experienced subjects: 48-week results of the VICTOR-E1 phase 2 trial.
abstract: BACKGROUND
  Agents that block the CCR5 coreceptor for human immunodeficiency virus (HIV) have demonstrated potent antiretroviral activity. In early clinical studies, the CCR5 antagonist vicriviroc proved to be a safe and effective component of combination antiretroviral therapy.
  
  
  METHODS
  This double-blind, dose-ranging, phase 2 trial randomized subjects to receive 30 mg or 20 mg of vicriviroc or placebo once daily plus re-optimized background therapy containing a protease inhibitor with ritonavir. Subjects were adults infected with CCR5-tropic HIV who were experiencing failure of triple antiretroviral regimens. The primary end point was mean change in baseline log(10) HIV RNA level at 48 weeks, based on an intent-to-treat analysis.
  
  
  RESULTS
  One hundred fourteen persons received vicriviroc at 30 mg (n = 39), vicriviroc at 20 mg (n =40), or placebo (n = 35). The mean change in baseline HIV RNA level at week 48 was -1.77 log(10) copies/mL for 30 mg of vicriviroc and -1.75 log(10) copies/mL for 20 mg of vicriviroc, compared with -0.79 log(10) copies/mL for placebo (P =.002 and P=.003, respectively, compared with placebo). Mean CD4 counts increased by 102, 136, and 63 cells/mm(3) for 30 mg vicriviroc, 20 mg vicriviroc, and placebo, respectively (P = .260 and P = .039, respectively, compared with placebo). Rates of adverse events (mostly mild-to-moderate) were 111.4, 112.5, and 147.4 events per 100 subject-years, respectively.
  
  
  CONCLUSIONS
  Vicriviroc administered with a protease inhibitor plus ritonavir-containing regimen shows potent antiretroviral and immunologic activity sustained over 48 weeks in treatment-experienced patients.
  
  
  BACKGROUND
  NCT00243230 .
authors.affiliation: Brasilmed Assistência Médica e Pesquisas, Federal University of Sao Paulo, Brazil.
authors.forename: Jamal
authors.initials: J
authors.lastname: Suleiman
authors.forename: Barry S
authors.initials: BS
authors.lastname: Zingman
authors.forename: Ricardo Sobhie
authors.initials: RS
authors.lastname: Diaz
authors.forename: Jose Valdez Ramalho
authors.initials: JV
authors.lastname: Madruga
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: Jihad
authors.initials: J
authors.lastname: Slim
authors.forename: Carmen
authors.initials: C
authors.lastname: Mak
authors.forename: Erin
authors.initials: E
authors.lastname: Lee
authors.forename: Michael C
authors.initials: MC
authors.lastname: McCarthy
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Dunkle
authors.forename: Sharon
authors.initials: S
authors.lastname: Walmsley
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D065100:CCR5 Receptor Antagonists; D018791:CD4 Lymphocyte Count; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D017320:HIV Protease Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D012367:RNA, Viral; D019438:Ritonavir; C486781:vicriviroc