Clinical Implications of Mutations at Reverse Transcriptase Codon 135 on Response to NNRTI-Based Therapy



Harout K Tossonian1, Jesse D Raffa2, Jason Grebely1, Mark Viljoen3, Annabel Mead3, Milan Khara3, Mark McLean3, Ashok Krishnamurthy3, Stanley DeVlaming3, Brian Conway*, 1
1 Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada
2 Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Canada
3 Pender Community Health Centre, Vancouver Coastal Health, Vancouver, Canada


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2007 Bentham Science Publishers Ltd.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/) which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the University of British Columbia, Department of Anesthesiology, Pharmacology and Therapeutics, 2176 Health Sciences Mall, Vancouver, BC, V6T1Z3, Canada; Tel: 604-822-7684; Fax: 604-822-6012; E-mail: bconway@interchange.ubc.ca


Abstract

To evaluate the impact of mutations at reverse transcriptase codon 135 on treatment outcomes in patients receiving NNRTI-based antiretroviral therapy, a total of 68 patients (30 with and 38 without baseline mutations at codon 135) were evaluated. Median increases in CD4 counts were 135 and 90 cells/mm3 (p=0.32), virologic suppression (HIV RNA < 400 copies/mL) was achieved in 16 (53%) and 16 (42%) patients (p=0.50), while NNRTI resistance was detected in 10/14 (71%) and 16/22 (73%) in patients with and without mutations at codon 135, respectively. Patients who experienced a virologic breakthrough and had a baseline mutation at codon 135 were more likely to evolve a single NNRTI resistance mutation (8/14 vs 4/22, p=0.029) but less likely to evolve multiple NNRTI resistance mutations (2/14 vs 12/22, p = 0.033). Mutations at codon 135 do not affect response rates, but affect the pattern of development of NNRTI resistance mutations. This has important implications for the subsequent use of newer NNRTIs such as etravirine in salvage therapy.