title: Rilpivirine vs. efavirenz-based single-tablet regimens in treatment-naive adults: week 96 efficacy and safety from a randomized phase 3b study.
abstract: OBJECTIVE
  To compare efficacy, safety, tolerability, and patient-reported outcomes between two single-tablet regimens, rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF), in HIV-1-infected, treatment-naive adults.
  
  
  METHODS
  This was a phase 3b, 96-week, randomized, open-label, international, noninferiority trial.
  
  
  METHODS
  A total of 799 participants were randomized (1 : 1) to receive RPV/FTC/TDF or EFV/FTC/TDF. The primary efficacy endpoint evaluated proportions of participants with HIV-1 RNA less than 50 copies/ml using the Snapshot algorithm. Additional assessments included CD4 cell counts, genotypic/phenotypic resistance, adverse events, patient-reported outcomes, and quality of life questionnaires.
  
  
  RESULTS
  At week 96, trial completion rates were 80.2% (316/394; RPV/FTC/TDF) and 74.0% (290/392; EFV/FTC/TDF). Overall, RPV/FTC/TDF was noninferior to EFV/FTC/TDF [HIV-1 RNA <50 copies/ml: 77.9 vs. 72.4%, respectively; difference -5.5; 95%CI (-0.6, 11.5); P = 0.076]. RPV/FTC/TDF was significantly more efficacious compared with EFV/FTC/TDF in participants with baseline HIV-1 RNA equal to or less than 100 000 copies/ml (78.8 vs. 71.2%; P = 0.046) and in those with CD4 cell count greater than 200 cells/μl (80.6 vs. 73.0%; P = 0.018). There was no significant between-group difference in the CD4 cell count increase (278 ± 189 vs. 259 ± 191 cells/μl; P = 0.17). Few participants developed resistance after week 48 (1.0% RPV/FTC/TDF; 0.3% EFV/FTC/TDF). Compared with EFV/FTC/TDF, RPV/FTC/TDF was associated with fewer adverse event-related discontinuations (3.0 vs. 11.0%; P<0.001), significantly fewer adverse events due to central nervous system issues and rash, greater improvements in patient-reported symptoms, and significant improvements in the SF-12v2 quality of life questionnaire mental health composite score (P = 0.014).
  
  
  CONCLUSIONS
  In treatment-naive, HIV-1-infected participants, 96-week RPV/FTC/TDF treatment demonstrated noninferior efficacy and better tolerability than EFV/FTC/TDF.
authors.affiliation: aUniversity Medical Centre, Hamburg-Eppendorf, Infectious Diseases Unit, Hamburg, Germany bNational Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Roma, Italy cGilead Sciences, Inc., Foster City, California, USA dHospital Universitario La Paz, IdiPAZ, Madrid, Spain eUniversity of North Carolina, Chapel Hill, North Carolina, USA fMedical University of Vienna, Vienna, Austria gUniversity of Toronto, Toronto, Ontario, Canada hHoldsworth House Medical Practice, Sydney, Australia iNew York Hospital Queens, Flushing, New York, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: van Lunzen
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.forename: Calvin J
authors.initials: CJ
authors.lastname: Cohen
authors.forename: José R
authors.initials: JR
authors.lastname: Arribas
authors.forename: David A
authors.initials: DA
authors.lastname: Wohl
authors.forename: Armin
authors.initials: A
authors.lastname: Rieger
authors.forename: Anita
authors.initials: A
authors.lastname: Rachlis
authors.forename: Mark
authors.initials: M
authors.lastname: Bloch
authors.forename: Sorana
authors.initials: S
authors.lastname: Segal-Maurer
authors.forename: Will
authors.initials: W
authors.lastname: Garner
authors.forename: Danielle
authors.initials: D
authors.lastname: Porter
authors.forename: Matthew
authors.initials: M
authors.lastname: Bosse
authors.forename: David
authors.initials: D
authors.lastname: Piontkowsky
authors.forename: Susan K
authors.initials: SK
authors.lastname: Chuck
authors.forename: Shampa
authors.initials: S
authors.lastname: De-Oertel
mesh_terms: D000328:Adult; 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*; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D011788:Quality of Life / Q000523:psychology; D012367:RNA, Viral / Q000097:blood; D000068696:Rilpivirine / Q000008:administration & dosage* / Q000009:adverse effects*; D013607:Tablets / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D012367:RNA, Viral; D013607:Tablets; D000068696:Rilpivirine; C098320:efavirenz