title: Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment.
abstract: The aim of this study was to evaluate the efficacy of maraviroc along with darunavir/ritonavir, all once daily, for the treatment of antiretroviral-naive HIV-1 infected individuals.
  
  
  
  MODERN was a multicentre, double-blind, noninferiority, phase III study in HIV-1 infected, antiretroviral-naive adults with plasma HIV-1 RNA at least 1000 copies/ml and no evidence of reduced susceptibility to study drugs.
  
  
  
  At screening, participants were randomized 1 : 1 to undergo either genotypic or phenotypic tropism testing. Participants with CCR5-tropic HIV-1 were randomized 1 : 1 to receive maraviroc 150 mg once daily or tenofovir/emtricitabine once daily each with darunavir/ritonavir once daily for 96 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA less than 50 copies/ml (Food and Drug Administration snapshot algorithm) at Week 48. A substudy evaluated bone mineral density, body fat distribution and serum bone turnover markers.
  
  
  
  Seven hundred and ninety-seven participants were dosed (maraviroc, n = 396; tenofovir/emtricitabine, n = 401). The Data Monitoring Committee recommended early study termination due to inferior efficacy in the maraviroc group. At Week 48, the proportion of participants with HIV-1 RNA less than 50 copies/ml was 77.3% for maraviroc and 86.8% for tenofovir/emtricitabine [difference of -9.54% (95% confidence interval: -14.83 to -4.24)]. More maraviroc participants discontinued for lack of efficacy, which was not associated with non-R5 tropism or resistance. Discontinuations for adverse events, Category C events, Grade 3/4 adverse events and laboratory abnormalities were similar between groups.
  
  
  
  A once-daily nucleos(t)ide-sparing two-drug regimen of maraviroc and darunavir/ritonavir was inferior to a three-drug regimen of tenofovir/emtricitabine and darunavir/ritonavir in antiretroviral-naive adults.
authors: aICH-Study Center, Hamburg, Germany bViiV Healthcare, Brentford, UK cSt. Vincent's Hospital, Sydney, New South Wales, Australia dUniversity of Alabama at Birmingham, Alabama ePfizer Inc., New York, New York, USA fOspedale San Raffaele, Divisione di Malattie Infettive, Milan, Italy gViiV Healthcare, Research Triangle Park, North Carolina, USA hPfizer Inc., Sandwich, UK iDivision of Infectious Diseases, University of Cincinnati, Cincinnati, Ohio, USA jViiV Healthcare, London kThe Research Network, Sandwich, UK lPfizer Inc., Groton, Connecticut, USA.
authors: Hans-Jürgen
authors: HJ
authors: Stellbrink
authors: Eric
authors: E
authors: Le Fevre
authors: Andrew
authors: A
authors: Carr
authors: Michael S
authors: MS
authors: Saag
authors: Geoffrey
authors: G
authors: Mukwaya
authors: Silvia
authors: S
authors: Nozza
authors: Srinivas Rao
authors: SR
authors: Valluri
authors: Manoli
authors: M
authors: Vourvahis
authors: Alex R
authors: AR
authors: Rinehart
authors: Lynn
authors: L
authors: McFadyen
authors: Carl
authors: C
authors: Fichtenbaum
authors: Andrew
authors: A
authors: Clark
authors: Charles
authors: C
authors: Craig
authors: Annie F
authors: AF
authors: Fang
authors: Jayvant
authors: J
authors: Heera
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D010949:Plasma / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D000072230:Sustained Virologic Response; D016896:Treatment Outcome; D019562:Viral Load; D056189:Viral Tropism
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral