The Open Virology Journal
2007, 1 : 8-13Published online 2007 August 20. DOI: 10.2174/1874357900701010008
Publisher ID: TOVJ-1-8
REVIEW ARTICLE
Clinical Implications of Mutations at Reverse Transcriptase Codon 135 on Response to NNRTI-Based Therapy
2 Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, Canada
3 Pender Community Health Centre, Vancouver Coastal Health, Vancouver, Canada
* 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.