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N348I in HIV-1 reverse transcriptase decreases susceptibility to tenofovir and etravirine in combination with other resistance mutations.

Sluis-Cremer, Nicolasa; Moore, Katieb; Radzio, Jessicaa; Sonza, Secondob,c; Tachedjian, Gildab,c,d

doi: 10.1097/QAD.0b013e3283315697
Research Letters

We previously demonstrated that N348I in HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. However, both of these inhibitors are currently infrequently used in developed countries, and the impact of N348I on newer reverse transcriptase inhibitors, such as tenofovir and etravirine, is unknown. In this study, we demonstrate that N348I alone confers no resistance to tenofovir and low-level resistance to etravirine. However, N348I significantly decreases tenofovir susceptibility when combined with thymidine analogue mutations and etravirine susceptibility when combined with Y181C.

aUniversity of Pittsburgh School of Medicine, Department of Medicine, Division of Infectious Diseases, Pittsburgh, Pennsylvania, USA

bMolecular Interactions Group, Centre for Virology, Burnet Institute, Melbourne, Australia

cDepartment of Microbiology, Monash University, Clayton, Australia

dDepartment of Medicine, Monash University, Melbourne, Victoria, Australia.

Received 8 June, 2009

Revised 19 July, 2009

Accepted 29 July, 2009

Correspondence to Gilda Tachedjian, PhD, Molecular Interactions Group, Centre for Virology, Burnet Institute, GPO Box 2284, Melbourne, VIC 3001, Australia. Tel: +61 3 9282 2256; fax: +61 3 9282 2100; e-mail: gildat@burnet.edu.au

© 2010 Lippincott Williams & Wilkins, Inc.