title: 96-Week resistance analyses of rilpivirine in treatment-naive, HIV-1-infected adults from the ECHO and THRIVE Phase III trials.
abstract: BACKGROUND
  In the ECHO/THRIVE 96-week efficacy analysis, the response rate was 78% with rilpivirine (RPV) and efavirenz (EFV) plus two nucleoside/nucleotide reverse transcriptase inhibitors.
  
  
  METHODS
  For resistance analyses, virological failures (VFs) were genotyped and/or phenotyped at baseline and failure.
  
  
  RESULTS
  In the overall 96-week resistance analyses, the proportion of VFs was higher with RPV (96/686, 14%) versus EFV (52/682, 8%), but similar within weeks 48-96 (22/686, 3% versus 16/682, 2%). In genotyped VFs, treatment-emergent non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) were as common with RPV (46/86, 53%) versus EFV (20/42, 48%), but nucleoside/nucleotide reverse transcriptase inhibitor RAMs were more common with RPV (48/86, 56%) than EFV (11/42, 26%). In RPV VFs, E138K+M184I remained the most frequent combination. Among RPV VFs with phenotypic RPV resistance, cross-resistance was observed with nevirapine (16/35, 46%), EFV (30/35, 86%) and etravirine (32/35, 91%). Among patients with baseline viral load (VL)≤100,000 copies/ml, there were fewer VFs (RPV: 28/368, 8%; EFV: 20/329, 6%), fewer VFs with treatment-emergent NNRTI RAMs (RPV: 10/27, 37%; EFV: 6/17, 35%), and less phenotypic resistance to RPV and other NNRTIs, than in patients with baseline VL>100,000 copies/ml (VFs: 68/318, 21% [RPV], 32/353, 9% [EFV]; NNRTI RAMs: 36/59, 61% [RPV], 14/32, 56% [EFV]). Among RPV VFs with baseline VL≤100,000 copies/ml observed within weeks 48-96, only 1/7 had phenotypic resistance to RPV.
  
  
  CONCLUSIONS
  During the second year of treatment in ECHO/THRIVE, few VFs with emerging NNRTI RAMs (no new RPV RAMs) occurred.
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium. lrimsky@its.jnj.com.
authors.forename: Laurence
authors.initials: L
authors.lastname: Rimsky
authors.forename: Veerle
authors.initials: V
authors.lastname: Van Eygen
authors.forename: Annemie
authors.initials: A
authors.lastname: Hoogstoel
authors.forename: Marita
authors.initials: M
authors.lastname: Stevens
authors.forename: Katia
authors.initials: K
authors.lastname: Boven
authors.forename: Gaston
authors.initials: G
authors.lastname: Picchio
authors.forename: Johan
authors.initials: J
authors.lastname: Vingerhoets
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D048588:Benzoxazines / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D009154:Mutation / Q000235:genetics; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000068696:Rilpivirine; D019562:Viral Load / Q000187:drug effects*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D000068696:Rilpivirine; C098320:efavirenz