Complexity of cross-resistance mutation patterns in diarylpyrimidine non-nucleoside reverse transcriptase inhibitors rilpivirine and etravirine in clinical isolates

Rilpivirine (RPV) and etravirine (ETR) are diarylpyrimidine non-nucleoside reverse transcriptase inhibitors (NNRTI) with a broad spectrum of anti-HIV activity against viruses resistant to nevirapine and efavirenz (EFV). To better understand the mechanism of diarylpyrimidine resistance, we analysed c...

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Published in:Antiviral therapy 2013-01, Vol.18, p.A110-A110
Main Authors: Matsuoka, K, Tanabe, F, Shigemi, U, Hattori, J, Ode, H, Masaoka, T, Morishita, R, Sawasaki, T, Yokomaku, Y, Iwatani, Y, Sugiura, W
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Language:English
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Human immunodeficiency virus
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Summary:Rilpivirine (RPV) and etravirine (ETR) are diarylpyrimidine non-nucleoside reverse transcriptase inhibitors (NNRTI) with a broad spectrum of anti-HIV activity against viruses resistant to nevirapine and efavirenz (EFV). To better understand the mechanism of diarylpyrimidine resistance, we analysed cross-resistance mutation patterns of RPV, ETR and EFV using an inhouse enzymatic reverse transcriptase (RT) assay. HIV RT DNA templates were prepared from 19 NL4-3 based clones with different combinations of 11 NNRTI resistance-associated mutations (RAM) introduced by site-directed mutagenesis and 31 patientderived isolates with different patterns of NNRTI RAM. The complexity of cross-resistance patterns of new NNRTIs, ETR and RPV, was shown by enzymatic RT assay. Because of the flexible structures of these two new NNRTIs, understanding their binding mode requires further mapping of minor resistance mutations.
ISSN:1359-6535