title: Efficacy and safety of lersivirine versus etravirine for the treatment of HIV-1 infection in patients with prior non-nucleoside reverse transcriptase inhibitor (NNRTI) use and evidence of NNRTI resistance: a randomized phase 2B trial.
abstract: OBJECTIVE
  To assess the efficacy and safety of lersivirine versus etravirine in patients with HIV-1 and prior non-nucleoside reverse transcriptase inhibitor (NNRTI) use and evidence of NNRTI resistance.
  
  
  METHODS
  In this 96-week, phase 2b study, 97 patients were randomized and treated with lersivirine 750 mg qd (n = 31), lersivirine 1,000 mg qd (n = 32), and etravirine 200 mg bid (n = 34), plus one optimized nucleoside reverse transcriptase inhibitor and darunavir/ritonavir 600/100 mg bid. The primary endpoint was the percentage of patients with HIV-1 RNA <50 copies/mL at week 24.
  
  
  RESULTS
  At week 24, HIV-1 RNA <50 copies/mL was achieved by fewer patients receiving lersivirine 750 mg (48.4%) and 1,000 mg (43.8%) qd compared with etravirine 200 mg qd (67.7%) (intention to treat [ITT], missing/switch/discontinuation equals failure [MSDF]). At week 48, HIV-1 RNA <50 copies/mL and <400 copies/mL were also achieved by fewer patients receiving lersivirine 750 mg (41.9% and 41.9%, respectively) and 1,000 mg (31.3% and 34.4%, respectively) qd compared with etravirine 200 mg bid (61.8% and 70.6%, respectively) (ITT, MSDF). Least squares means (SE) change from baseline in log transformed HIV-1 RNA at week 48 was -1.42 (0.27) and -0.95 (0.28) copies/mL for lersivirine 750 mg and 1,000 mg qd, respectively, versus -2.02 (0.26) copies/mL for etravirine 200 mg bid (ITT). Lersivirine and etravirine were generally safe and well-tolerated.
  
  
  CONCLUSIONS
  Lersivirine 750 mg and 1,000 mg qd was associated with lower rates of viral suppression at week 24 and week 48 versus etravirine in patients with prior NNRTI use and evidence of NNRTI resistance. No new safety signals were detected.
authors.affiliation: Orlando Immunology Center, Orlando, Florida, USA.
authors.forename: Edwin
authors.initials: E
authors.lastname: DeJesus
authors.affiliation: First Department of Internal Medicine, University of Cologne, Cologne, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Fätkenheuer
authors.affiliation: Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa.
authors.forename: Catherine
authors.initials: C
authors.lastname: Orrell
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Cunshan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Pfizer Inc, New York, New York, USA.
authors.forename: James
authors.initials: J
authors.lastname: Jones
authors.affiliation: The Research Network, Sandwich, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Craig
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Tawadrous
authors.affiliation: Pfizer Inc, Groton, Connecticut, USA.
authors.forename: Jayvant
authors.initials: J
authors.lastname: Heera
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011720:Pyrazoles; D011724:Pyridazines; D011743:Pyrimidines; C531151:UK 453,061; C451734:etravirine
keywords: HIV-1; NNRTI; efficacy; etravirine; lersivirine; safety