High rate of K65R for antiretroviral therapy-naive patients with subtype C HIV infection failing a tenofovir-containing first-line regimen

Abstract

OBJECTIVE: We sought to determine the rate of the K65R mutation in patients receiving tenofovir (TDF)-based antiretroviral therapy (ART) with subtype C HIV infection. DESIGN: Retrospective cohort study. METHODS: All patients initiated on stavudine (d4T) with lamivudine (3TC) or TDF with 3TC and a nonnucleoside reverse transcriptase inhibitor at McCord Hospital in Durban, South Africa had their charts reviewed. All patients with virologic failure, defined as a viral load more than 1000 copies/ml after 5 months of a first ART regimen, had genotypic resistance testing performed prospectively using a validated in-house assay. Important resistance mutations were selected based upon published mutations in subtype B virus in the Stanford HIV Drug Resistance database. RESULTS: A total of 585 patients were initiated on TDF-containing first-line ART from 3 August 2010 to 17 March 2011. Thirty-five (6.0%) of these patients had virologic failure and 23 of 33 (69.7%) of the virologic failure patients had the K65R mutation. The median (interquartile range) for the baseline CD4 cell count was 105 cells/μl (49-209) and viral load at virologic failure was 47 571 copies/ml (20 708-202 000). During the same period, 53 patients were initiated on d4T-containing regimens. Two (3.8%) of these patients had virologic failure and one of the virologic failure patients had the K65R mutation. CONCLUSION: Preliminary data show very high rates (>65%) of K65R for patients failing TDF-based first-line regimens at McCord Hospital with few additional nucleoside reverse transcriptase inhibitor mutations compared with subtype B. These rates may reflect faster in-vivo selection, longer time on a failing regimen or transmitted drug resistance.