Prevalence of etravirine resistance associated mutations in HIV‐1 strains isolated from infected individuals failing efavirenz: Comparison between subtype B and non‐B genetic variants

Abstract

Etravirine (ETR) is a non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) with a high genetic barrier to the development of resistance and with potential activity against Human immunodeficiency virus type 1 (HIV-1) strains resistant to first-generation NNRTIs. The objective of this study was to investigate the prevalence of ETR resistance associated mutations (RAMs) in HIV-1 strains isolated from infected individuals failing efavirenz (EFV), as well as to evaluate possible differences in the distribution of ETR RAMs between subtype B and non-B genetic variants. Nucleotide sequences of the protease and partial reverse transcriptase (RT) coding regions of the pol gene of 55 HIV-1 strains isolated from infected individuals failing EFV on regular follow-up at a reference center in Portugal, were retrospectively analyzed. The most prevalent ETR RAMs observed were L100I, V90I, and K101E, with a prevalence of 16.4% (n = 9), 9.1% (n = 5), and 5.5% (n = 3), respectively. Overall, 47.3% (n = 26) of the nucleotide sequences had at least one ETR RAM: 38.2% (n = 21) had one ETR RAM, 7.3% (n = 4) had two ETR RAMs and 1.8% (n = 1) had three ETR RAMs. No statistically significant differences were found in the distribution of ETR RAMs between subtype B and non-B genetic variants. The results demonstrate that ETR rescue therapy is a viable option in treatment-experienced individuals failing EFV and suggests that ETR may be equally useful in HIV-1 infections caused by different genetic variants.

HIV-1 Genetic Variability and Clinical Implications

“…A recent study highlighted the fact that HIV-1 genetic variant does not significantly influence the genotypic prediction of etravirine susceptibility in infected individuals failing efavirenz containing regimens [175]. However, among the etravirine resistance associated mutations, some polymorphic substitutions resulted in drug-naive individuals infected with non-B subtypes, especially CRF02_AG [176].…”