Open AccessGenotypic susceptibility to etravirine‐assessment in a population of NNRTI‐experienced patients
Author(s) -
Piñeiro C,
Xerinda S,
Figueiredo C,
Santos A,
Soares J,
Serrão R,
Sarmento A
Publication year - 2012
Publication title -
journal of the international aids society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.724
H-Index - 62
ISSN - 1758-2652
DOI - 10.7448/ias.15.6.18208
Subject(s) - etravirine , efavirenz , nevirapine , medicine , regimen , genotype , discontinuation , virology , drug resistance , hiv drug resistance , reverse transcriptase inhibitor , population , viral load , human immunodeficiency virus (hiv) , gastroenterology , antiretroviral therapy , biology , genetics , gene , environmental health
Background With the availability of the 2nd‐generation non‐nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (ETR), it is possible to obtain undetectable plasma viral load in HIV‐1‐infected treatment experienced patients with resistance mutations to NNRTIs. The purpose of this study is to determine the proportion of patients with prior exposure to NNRTIs who may benefit from a therapeutic regimen including ETR. Patients and methods Analysis of the genotypic resistance tests of patients having failed efavirenz (EFV) or nevirapine (NVP) antiretroviral‐based regimens, in a 5‐year period (2007–2011). Susceptibility to ETR was assessed using four different algorithms: HIVdb Stanford University HIV Drug Resistance Database, ANRS score, REGA score and Tibotec weighted genotypic score. Results Of 170 patients with a history of failure or abandonment of regimens containing EFV or NVP, 68 (40%) had mutations conferring resistance to these NNRTIs (RAMs). Resistance tests were carried out from seven months before to 3 years after (X=48±207 days) the NNRTIs discontinuation. Of the HIV‐1 subtypes identified (n=67), most were were subtype B (53.7%) and G (34.3%) RAMs found in the 68 samples successfuly genotyped: V90I (n=2), A98G (n=1), L100I (n=7), K101E (n=5), K103N (n=38), K103S (n=2), V106A (n=1), V106M (n=1), V108I (n=4), V179D (n=4), Y181C (n=18), Y188C (n=1), Y188H (n=1), G190A (n=11), G190E (n=1), G190S (n=1), H221Y (n=6), P225H (n=1), F227L (n=3) and K238T (n=2). In 27 (39.7%) patients only one RAM was detected, 30 (44.1%) had 2, 6 had three mutations and 5 other patients had more than three RAMs to NNRTIs. Susceptibility to ETR varied depending on the used algorithm:Susceptible Intermediate resistance ResistantANRS 60 (88.2%) 3 (4.4%) 5 (7.4%) HIVdb 49 (72.0%) 17 (25.0%) 2 (3.0%) REGA 40 (58.8%) 27 (39.7%) 1 (1.5%) Tibotec 44 (64.7%) 23 (33.8%) 1 (1.5%)Conclusion In this population with resistant virus to EFV and NVP, we found a low frequency of mutations conditioning severely impacting on susceptibility to ETR. Based on these results, ETR could be a useful component of effective treatment regimens for the majority of these patients with prior exposure to 1st‐generation NNRTIs.