Resistance analyses in highly experienced patients failing raltegravir, etravirine and darunavir/ritonavir regimen.
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.
Charpentier
Charlotte
C
Hôpital Bichat-Claude Bernard, Université Paris-Diderot, France.
Roquebert
Bénédicte
B
Colin
Céline
C
Taburet
Anne-Marie
AM
Fagard
Catherine
C
Katlama
Christine
C
Molina
Jean-Michel
JM
Jacomet
Christine
C
Brun-Vézinet
Françoise
F
Chêne
Geneviève
G
Yazdanpanah
Yazdan
Y
Descamps
Diane
D
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
D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D013449:Sulfonamides; C451734:etravirine; D019438:Ritonavir; D000069454:Darunavir