title: Maraviroc once-daily nucleoside analog-sparing regimen in treatment-naive patients:  randomized, open-label pilot study.
abstract: OBJECTIVE
  This study was performed to evaluate a once-daily dual-therapy regimen, maraviroc (MVC) + atazanavir/ritonavir (ATV/r), in treatment-naive patients.
  
  
  METHODS
  A phase 2b, randomized, open-label pilot study.
  
  
  METHODS
  In Study A4001078 (NCT00827112), treatment-naive patients with CCR5-tropic HIV-1 (HIV-1 RNA ≥1000 copies/mL; CD4 cell count ≥100 cells/mm) were randomized to receive either MVC 150 mg once daily (n = 60) or tenofovir/emtricitabine (TDF/FTC) 300/200 mg once daily (n = 61) + ATV/r 300/100 mg once daily. Primary endpoint was proportion of patients with HIV-1 RNA <50 copies per milliliter at week 48.
  
  
  RESULTS
  At week 48, 44 (74.6%) and 51 (83.6%) patients in the MVC and TDF/FTC treatment groups, respectively, had plasma HIV-1 RNA <50 copies per milliliter. Median change from baseline in CD4 cell count at week 48 was +173 and +187 cells per cubic millimeter with MVC and TDF/FTC, respectively. Seven patients discontinued from each arm; there were no deaths. The incidence of serious adverse events (AEs) was similar in each group; however, there were more grade 3/4 AEs in the MVC group (18 vs 11), mostly due to hyperbilirubinemia. Three patients in each arm were evaluable for virological analysis at discontinuation or failure (HIV-1 RNA >500 copies/mL); no genotypic resistance, change in tropism, or loss of susceptibility relevant to treatment was observed.
  
  
  CONCLUSIONS
  The virological activity and immunological benefit of once-daily MVC + ATV/r were confirmed. Indirect hyperbilirubinemia and associated signs were the most commonly reported AEs in both study treatment groups and were not associated with significant transaminase increases. No drug resistance occurred.
authors.affiliation: Anthony Mills MD Inc., Los Angeles, CA, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Mills
authors.forename: Donna
authors.initials: D
authors.lastname: Mildvan
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
authors.forename: Soe
authors.initials: S
authors.lastname: Than
authors.forename: Srinivas R
authors.initials: SR
authors.lastname: Valluri
authors.forename: Charles
authors.initials: C
authors.lastname: Craig
authors.forename: Lynn
authors.initials: L
authors.lastname: McFadyen
authors.forename: Manoli
authors.initials: M
authors.lastname: Vourvahis
authors.forename: Jayvant
authors.initials: J
authors.lastname: Heera
authors.forename: Hernan
authors.initials: H
authors.lastname: Valdez
authors.forename: Alex R
authors.initials: AR
authors.lastname: Rinehart
authors.forename: Simon
authors.initials: S
authors.lastname: Portsmouth
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000069446:Atazanavir Sulfate; D065100:CCR5 Receptor Antagonists; D018791:CD4 Lymphocyte Count; D003510:Cyclohexanes / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects; D000068679:Emtricitabine; D005260:Female; D023581:HIV Fusion Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use; D010865:Pilot Projects; D011725:Pyridines / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood*; D019438:Ritonavir / Q000627:therapeutic use; D000068698:Tenofovir; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D012367:RNA, Viral; D014230:Triazoles; D003841:Deoxycytidine; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D000077592:Maraviroc; D019438:Ritonavir