title: Efficacy and safety of lersivirine (UK-453,061) versus efavirenz in antiretroviral treatment-naive HIV-1-infected patients: week 48 primary analysis results from an ongoing, multicenter, randomized, double-blind, phase IIb trial.
abstract: OBJECTIVE
  A 96-week clinical study was planned to estimate the antiviral activity and safety of lersivirine in treatment-naive HIV-1-infected patients.
  
  
  METHODS
  This ongoing international, multicenter, double-blind, randomized, Phase IIb exploratory study evaluates the efficacy and safety of 2 doses of lersivirine or 1 of efavirenz, each combined with tenofovir disoproxil fumarate/emtricitabine. Patients were randomized 1:1:1 to receive lersivirine (500 or 750 mg once daily) or efavirenz (600 mg once daily), each administered with tenofovir disoproxil fumarate/emtricitabine (300 mg/200 mg, once daily). The primary endpoint is the proportion of patients with HIV-1 RNA <50 copies per milliliter (missing/discontinuation = failure) at week 48.
  
  
  RESULTS
  For the 193 patients in the study, baseline mean plasma HIV-1 RNA was 4.7 log10 copies per milliliter, and median CD4 cell count was 312 cells per cubic millimeter. At week 48, the percentage of patients with HIV-1 RNA <50 copies per milliliter was 78.5% (51/65), 78.5% (51/65), and 85.7% (54/63) in the lersivirine 500 mg, 750 mg, and efavirenz groups, respectively. CD4 cell count changes from baseline were similar across groups. Virologic failure occurred in 7 patients (11%) in each of the lersivirine groups and 3 patients (5%) in the efavirenz group. The pattern of lersivirine resistance was distinct from other nonnucleoside reverse transcriptase inhibitors. Overall incidences of all-causality treatment-related or grade 3/4 adverse events (AEs) or AE-related discontinuations were lower with lersivirine than with efavirenz, and serious AEs occurred at similar rates across treatment groups.
  
  
  CONCLUSIONS
  Both lersivirine doses showed broadly comparable efficacy to efavirenz over 48 weeks in treatment-naive patients, with different AE profiles from efavirenz.
authors: Cantonal Hospital, St. Gallen, Switzerland. pietro.vernazza@kssg.ch
authors: Pietro
authors: P
authors: Vernazza
authors: Cunshan
authors: C
authors: Wang
authors: Anton
authors: A
authors: Pozniak
authors: Elizabeth
authors: E
authors: Weil
authors: Piotr
authors: P
authors: Pulik
authors: David A
authors: DA
authors: Cooper
authors: Richard
authors: R
authors: Kaplan
authors: Adriano
authors: A
authors: Lazzarin
authors: Hernan
authors: H
authors: Valdez
authors: James
authors: J
authors: Goodrich
authors: Julie
authors: J
authors: Mori
authors: Charles
authors: C
authors: Craig
authors: Margaret
authors: M
authors: Tawadrous
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D048588:Benzoxazines / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination / Q000009:adverse effects; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D063065:Organophosphonates / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D000068698:Tenofovir; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D063065:Organophosphonates; D011720:Pyrazoles; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C531151:UK 453,061; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; C098320:efavirenz