title: A 48-week randomized phase 2b study evaluating cenicriviroc versus efavirenz in treatment-naive HIV-infected adults with C-C chemokine receptor type 5-tropic virus.
abstract: OBJECTIVE
  To compare the efficacy, safety, and anti-inflammatory effects of cenicriviroc (CVC), an oral, once-daily C-C chemokine receptor types 5 and 2 antagonist, with those of efavirenz (EFV) in treatment-naive, HIV-1-infected adults.
  
  
  METHODS
  A 48-week, randomized, double-blind, double-dummy phase 2b trial at 43 institutions (USA and Puerto Rico).
  
  
  METHODS
  Study participants (HIV-1 RNA ≥1000 copies/ml, CD4 cell count ≥200 cells/μl, C-C chemokine receptor type 5-tropic virus) were randomized 2 : 2 : 1 to CVC 100 mg (CVC100), CVC 200 mg (CVC200), or EFV 600 mg, each administered with emtricitabine/tenofovir disoproxil fumarate. Key end points were virologic success (HIV-1 RNA <50 copies/ml) at week 24 (primary) and week 48 (secondary), safety/tolerability at weeks 24 and 48. Study sites and patients remained blinded until week 48.
  
  
  RESULTS
  A total of 143 patients were randomized (CVC100, n = 59; CVC200, n = 56; EFV, n = 28). Virologic success was obtained at week 24 in 76, 73, and 71% of study participants for CVC100, CVC200, and EFV, respectively (all P > 0.05 versus EFV), and at week 48 in 68, 64, and 50%, respectively (all P > 0.05 versus EFV). Resistance mutations emerged in five and zero CVC and EFV-treated study participants, respectively. Virologic nonresponse and nucleoside reverse transcriptase inhibitor resistance decreased when CVC minimum plasma concentration was at least 47.8 ng/ml. Treatment-related adverse events of at least grade 2 and discontinuations because of adverse events were less frequent in CVC-treated study participants. Total and low-density lipoprotein cholesterol decreased with CVC, but increased with EFV. C-C chemokine ligand type 2 (CCL2) (aka monocyte chemotactic protein-1) increased in a dose-dependent manner, whereas soluble CD14 levels decreased with CVC.
  
  
  CONCLUSIONS
  CVC showed efficacy and favorable safety in treatment-naive HIV-1-infected study participants, supporting selection of CVC200 for phase 3 studies.
  
  
  BACKGROUND
  NCT01338883.
authors.affiliation: aAIDS Research Consortium of Atlanta, Atlanta, Georgia bUniversity of Alabama at Birmingham, Birmingham, Alabama cOrlando Immunology Center, Orlando, Florida dTherapeutic Concepts, Houston, Texas eQuest Clinical Research, San Francisco, California fRush University, Chicago, Illinois gNevada AIDS Research and Education Society, Las Vegas, Nevada hTobira Therapeutics, Inc., South San Francisco, California iUniversity of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Thompson
authors.forename: Michael
authors.initials: M
authors.lastname: Saag
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.forename: Joseph
authors.initials: J
authors.lastname: Gathe
authors.forename: Jay
authors.initials: J
authors.lastname: Lalezari
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: Jerry
authors.initials: J
authors.lastname: Cade
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Enejosa
authors.forename: Eric
authors.initials: E
authors.lastname: Lefebvre
authors.forename: Judith
authors.initials: J
authors.lastname: Feinberg
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011647:Puerto Rico; D054380:Receptors, CXCR5 / Q000037:antagonists & inhibitors*; D015728:Receptors, HIV / Q000037:antagonists & inhibitors; D013454:Sulfoxides; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load; D056189:Viral Tropism; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; C095085:CXCR5 protein, human; D003521:Cyclopropanes; D007093:Imidazoles; D007155:Immunologic Factors; D054380:Receptors, CXCR5; D015728:Receptors, HIV; D013454:Sulfoxides; C506967:cenicriviroc; C098320:efavirenz