HIV protease and reverse transcriptase variation and therapy outcome in antiretroviral-naive individuals from a large North American cohort

Objective: To assess the effect of baseline HIV reverse transcriptase (RT) and protease sequence variation on virologic outcomes in a large cohort of antiretroviral-naive patients in British Columbia, Canada. Methods: Population sequencing of RT and protease was performed on baseline viral RNA of all antiretroviral-naive patients first seeking treatment in British Columbia between lune 1997 and August 1998 (n = 479). Relative risks of virological failure associated with genotypic differences from a 'standard' HIV strain (HXB2) were assessed for up to 18 months. Results: The prevalence of key baseline mutations known to confer resistance to RT and protease inhibitors (PI) was 3.4 and 3.8%, respectively. No statistically significant impact on virologic outcomes could be established for these patients. However, the data suggest that some individuals (harboring a M184V mutation in RT or a V821 in protease) may have benefited from pre-therapy resistance tests. 'Secondary' mutations in the protease associated with resistance (e.g. codons 10, 36 or 63) were common, but the presence of these secondary mutations, either alone or in combination, did not appear to result in early loss of therapeutic virological suppression. Preliminary analyses suggest that an amino acid change at codon 35 in the protease may be associated with early treatment failure. Conclusions: The results suggest that routine genotyping of naive patients about to start antiretroviral therapy would be of benefit to a relatively small proportion of the population. Secondary mutations associated with resistance to PI alone were not found to affect virologic outcomes significantly. (C) 2001 Lippincott Williams & Wilkins.