Characterization of the E138K Resistance Mutation in HIV-1 Reverse Transcriptase Conferring Susceptibility to Etravirine in B and Non-B HIV-1 Subtypes

• DOI: 10.1128/aac.01192-10
• Publication Date: 2010-12-07T06:29:34Z
• Authors: Eugene L. Asahchop; Maureen Oliveira; Mark A. Wainberg; Bluma G. Brenner; Daniela Moisi; Thomas d'Aquin Toni; Cecile L. Tremblay
• Keywords: Etravirine; Efavirenz

ABSTRACT We have selected for resistance to etravirine (ETR) and efavirenz (EFV) in tissue culture using three subtype B, C, two CRF02_AG clinical isolates, grown cord blood mononuclear cells. Genotypic analysis was performed at baseline various weeks of selection. Phenotypic regard ETR, EFV, nevirapine (NVP) evaluated 25 30 all ETR-selected viruses viral clones that contained specific mutations were inserted by site-directed mutagenesis into pNL-4.3 AG plasmids. The results show ETR positions V90I, K101Q, E138K, V179D/E/F, Y181C, V189I, G190E, H221H/Y, M230L E138K the first these emerge most instances. time emergence longer case (18 weeks) compared EFV (11 weeks), no differences patterns emergent could be documented between B non-B subtypes. Viral containing displayed low-level phenotypic (3.8-fold) modestly impaired replication capacity (2-fold) wild-type virus. virus showed a high degree cross-resistance NVP but not EFV. identified V179E, H221Y as included among 17 currently recognized resistance-associated ETR.