title: Week 96 analysis of rilpivirine or efavirenz in HIV-1-infected patients with baseline viral load ≤ 100 000 copies/mL in the pooled ECHO and THRIVE phase 3, randomized, double-blind trials.
abstract: OBJECTIVE
  These 96-week, ECHO/THRIVE pooled analyses evaluated data for antiretroviral treatment-naïve, HIV-1-infected adults with viral load (VL) ≤ 100 000 HIV-1 RNA copies/mL receiving rilpivirine or efavirenz.
  
  
  METHODS
  ECHO and THRIVE were phase 3, randomized, double-blind trials. Patients received rilpivirine 25 mg once daily (qd) or efavirenz 600 mg qd, with a fixed (ECHO) or investigator-chosen (THRIVE) nucleoside/tide reverse transcriptase inhibitor (N[t]RTI) background regimen. Response rate (the percentage of patients with VL < 50 copies/mL, using an intent-to-treat-population, time-to-loss-of-virological-response algorithm), virological failure (VF), resistance development, safety and tolerability were evaluated.
  
  
  RESULTS
  Baseline characteristics were comparable between the rilpivirine (n = 368) and efavirenz (n = 329) groups. At week 96, response rates [84% for rilpivirine vs. 80% for efavirenz; difference 4.0%; 95% confidence interval (CI) -1.7% to 9.7%] and incidences of VF for the resistance analysis (VFres) (8% for rilpivirine vs. 6% for efavirenz; P = 0.46) were similar in the two groups. Among patients with VFres , a comparable proportion in each group developed nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs). Among those with VFres , more patients in the rilpivirine group than in the efavirenz group developed N[t]RTI RAMs, mostly M184I/V. The mean (95% CI) CD4 cell count increased from baseline to week 96 by 224 (208-240) cells/μL in the rilpivirine group and by 206 (188-225) cells/μL in the efavirenz group. Treatment-related grade 2-4 overall adverse events, any rash and dizziness were less frequent for rilpivirine than for efavirenz (P < 0.0001).
  
  
  CONCLUSIONS
  Rilpivirine demonstrated antiviral efficacy similar to that of efavirenz in antiretroviral treatment-naïve adults with baseline VL ≤ 100 000 copies/mL over 96 weeks. Frequencies of VFres and emergent NNRTI RAMs in each group were similar. More patients with VFres in the rilpivirine group than in the efavirenz group developed N[t]RTI RAMs (mostly M184I/V). Rilpivirine had a more favourable safety/tolerability profile than efavirenz.
authors: Department of Infectious Diseases, Saint Louis Hospital-APHP, INSERM U941 and University of Paris Diderot, Paris, France.
authors: J-M
authors: JM
authors: Molina
authors: N
authors: N
authors: Clumeck
authors: C
authors: C
authors: Orkin
authors: L T
authors: LT
authors: Rimsky
authors: S
authors: S
authors: Vanveggel
authors: M
authors: M
authors: Stevens
mesh_terms: D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000627:therapeutic use*; D003521:Cyclopropanes; D004311:Double-Blind Method; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008297:Male; D009570:Nitriles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D000068696:Rilpivirine; D019562:Viral Load / Q000187:drug effects
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D000068696:Rilpivirine; C098320:efavirenz
keywords: TMC278; baseline viral load; efavirenz; nonnucleoside reverse transcriptase inhibitor; rilpivirine; treatment-naïve