title: Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: pooled results from the phase 3 double-blind randomized ECHO and THRIVE Trials.
abstract: BACKGROUND
  Pooled analysis of phase 3, double-blind, double-dummy ECHO and THRIVE trials comparing rilpivirine (TMC278) and efavirenz.
  
  
  METHODS
  Treatment-naive HIV-1-infected adults were randomized 1:1 to rilpivirine 25 mg once daily or efavirenz 600 mg once daily, with background tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) (ECHO) or TDF/FTC, zidovudine/lamivudine, or abacavir/lamivudine (THRIVE). The primary endpoint was confirmed response [viral load <50 copies per milliliter; intent-to-treat time-to-loss-of-virologic-response (ITT-TLOVR) algorithm] at week 48. The pooled data set enabled analyses of subgroups and predictors of response/virologic failure.
  
  
  RESULTS
  Confirmed responses were 84% (rilpivirine) and 82% (efavirenz). The difference in response rates (95% confidence interval) was 2.0% (-2.0% to 6.0%). The incidence of virologic failure was 9% (rilpivirine) versus 5% (efavirenz). Responses in ITT-TLOVR and ITT-snapshot analyses were consistent. Responses were similar for rilpivirine and efavirenz by background regimen, gender, race and clade. Suboptimal adherence and higher baseline viral load resulted in lower responses, higher virologic failure, and development of resistance in both groups; the effects on virologic failure were more apparent with rilpivirine. CD4 cell count increased over time in both groups. Rilpivirine compared with efavirenz gave smaller incidences of adverse events leading to discontinuation (3% vs. 8%, respectively), treatment-related grade 2-4 adverse events (16% vs. 31%), rash (3% vs. 14%), dizziness (8% vs. 26%), abnormal dreams/nightmares (8% vs. 13%), and grade 2-4 lipid abnormalities.
  
  
  CONCLUSIONS
  At week 48, rilpivirine 25 mg once daily and efavirenz 600 mg once daily had comparable response rates. Rilpivirine had more virologic failures and improved tolerability versus efavirenz.
authors.affiliation: Community Research Initiative of New England, Boston, MA, USA. ccohen@crine.org
authors.forename: Calvin J
authors.initials: CJ
authors.lastname: Cohen
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Jan
authors.initials: J
authors.lastname: Fourie
authors.forename: Beatriz
authors.initials: B
authors.lastname: Grinsztejn
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Johnson
authors.forename: Michael
authors.initials: M
authors.lastname: Saag
authors.forename: Khuanchai
authors.initials: K
authors.lastname: Supparatpinyo
authors.forename: Herta
authors.initials: H
authors.lastname: Crauwels
authors.forename: Eric
authors.initials: E
authors.lastname: Lefebvre
authors.forename: Laurence T
authors.initials: LT
authors.lastname: Rimsky
authors.forename: Simon
authors.initials: S
authors.lastname: Vanveggel
authors.forename: Peter
authors.initials: P
authors.lastname: Williams
authors.forename: Katia
authors.initials: K
authors.lastname: Boven
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D048588:Benzoxazines / Q000008:administration & dosage* / Q000009:adverse effects; D003521:Cyclopropanes; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D000068696:Rilpivirine; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D011743:Pyrimidines; D000068696:Rilpivirine; C098320:efavirenz