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Evaluation of etravirine resistance in clinical samples by a simple phenotypic Test
Author(s) -
Agneskog Eva,
Nowak Piotr,
Källander Clas F.R.,
Sönnerborg Anders
Publication year - 2013
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.23507
Subject(s) - virology , drug resistance , etravirine , reverse transcriptase , hiv drug resistance , reverse transcriptase inhibitor , genotype , recombinant dna , biology , drug , virus , medicine , gene , polymerase chain reaction , pharmacology , viral load , antiretroviral therapy , microbiology and biotechnology , genetics
Drug resistance testing is an important tool in the management of HIV‐1 infection. As access to genotypic resistance assays is limited in low‐ and middle‐income settings, alternatives are warranted. The aim of the study was to adapt a phenotypic drug susceptibility assay, ExaVir Drug, for detection of resistance to the second generation non‐nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (ETR). Five NNRTI resistant mutant forms of RT were produced (L100I, K103N, L100I/K103N, Y181C, V179D) in order to validate the assay for ETR. Furthermore, HIV‐1 RT was purified from plasma samples (n = 28) obtained from treatment naïve and experienced HIV‐1 infected patients, and ETR drug susceptibility (IC 50 ) was estimated. The direct sequencing of the pol gene was performed. The recombinant RT mutants had the expected changes in drug sensitivity patterns. The RTs isolated from plasma of therapy naïve individuals showed low IC 50 for ETR. In the plasma virus from treatment experienced patients with Y181C, A98G, V108I, and/or K101E mutations in the pol gene, higher IC 50 values were found in line with reduced susceptibility data for ETR. This study demonstrates that ExaVir® Drug, a simple enzymatic phenotypic assay, can be used for detection of ETR resistance, including cross‐resistance to other NNRTIs, in clinical samples. A further evaluation is needed to define clinical cut‐offs; however the assay is an alternative to more costly HIV drug resistance tests, especially in low‐income countries. J. Med. Virol. 85:703–708, 2013. © 2013 Wiley Periodicals, Inc.