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 risk s of virological failure associated with genotypic differences from a 'stan dard' HIV strain (HXB2) were assessed for up to 18 months. Results: The prevalence of key baseline mutations known to confer resistanc e to RT and protease inhibitors (PI) was 3.4 and 3.8%, respectively. No sta tistically significant impact on virologic outcomes could be established fo r these patients. However, the data suggest that some individuals (harborin g 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 o f these secondary mutations, either alone or in combination, did not appear to result in early loss of therapeutic virological suppression. Preliminar y analyses suggest that an amino acid change at codon 35 in the protease ma y 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 s mall proportion of the population. Secondary mutations associated with resi stance to PI alone were not found to affect virologic outcomes significantl y. (C) 2001 Lippincott Williams & Wilkins.