title: Resistance analyses in highly experienced patients failing raltegravir, etravirine and darunavir/ritonavir regimen.
abstract: OBJECTIVE
  ANRS 139 TRIO trial was a phase II noncomparative trial that evaluated in highly experienced patients, a combination of raltegravir, etravirine and darunavir boosted with ritonavir. We analyzed emergence of resistant viruses at the time of virological failure and investigated the impact of baseline integrase polymorphisms on virological failure occurrence.
  
  
  METHODS
  Bulk sequencing of protease, reverse transcriptase and integrase genes was performed for 103 patients at baseline and 14 patients at the time of virological failure. Additionally, integrase clonal analyses were performed at baseline and at virological failure in patients with successful integrase gene amplification. Impact of baseline integrase polymorphisms on virological failure occurrence was analyzed using Fisher exact and Wilcoxon tests.
  
  
  RESULTS
  In the 14 failing patients median viral load at virological failure was 90 copies/ml (interquartile range = 60-783). Emergence of darunavir and etravirine resistance mutations was observed at virological failure in only one and three patients, respectively. Raltegravir resistance mutations were found neither at baseline nor at the time of virologic failure. Integrase clonal analyses showed neither the presence nor the selection of minority variants carrying raltegravir resistance mutations at baseline or at virological failure. No impact of baseline integrase polymorphisms was observed on virological failure either at week 24 or at week 48.
  
  
  CONCLUSIONS
  Virological failure occurred in a small proportion of patients with low viral load. No raltegravir resistance mutations were observed using bulk sequencing or clonal analyses, and darunavir and etravirine resistance-associated mutations were detected in only one and three patients, respectively at virological failure. No impact of baseline integrase polymorphism was observed on virological failure occurrence.
authors.affiliation: Hôpital Bichat-Claude Bernard, Université Paris-Diderot, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Roquebert
authors.forename: Céline
authors.initials: C
authors.lastname: Colin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Taburet
authors.forename: Catherine
authors.initials: C
authors.lastname: Fagard
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Christine
authors.initials: C
authors.lastname: Jacomet
authors.forename: Françoise
authors.initials: F
authors.lastname: Brun-Vézinet
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
authors.forename: Yazdan
authors.initials: Y
authors.lastname: Yazdanpanah
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D000069454:Darunavir; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D009570:Nitriles; D011724:Pyridazines / Q000494:pharmacology*; D011743:Pyrimidines; D019438:Ritonavir / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D013449:Sulfonamides; C451734:etravirine; D019438:Ritonavir; D000069454:Darunavir