Genotypic susceptibility to etravirine‐assessment in a population of NNRTI‐experienced patients
In: Journal of the International AIDS Society, Band 15, Heft S4, S. 1-1
ISSN: 1758-2652
BackgroundWith 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 methodsAnalysis 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.ResultsOf 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
Resistant
ANRS
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%)
ConclusionIn 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.