"Dynamic range" of inferred phenotypic HIV drug resistance values in clinical practice.

Abstract

'Virtual' or inferred phenotypes (vPhenotypes) are commonly used to assess resistance to antiretroviral agents in patients failing therapy. In this study, we provide a clinical context for understanding vPhenotype values. All HIV-infected persons enrolled in the British Columbia Drug Treatment Program with a baseline plasma viral load (pVL) and follow-up genotypic resistance and pVL results were included up to October 29, 2008 (N = 5,277). Change from baseline pVL was determined as a function of Virco vPhenotype, and the "dynamic range" (defined here by the 10th and 90th percentiles for fold-change in IC₅₀ amongst all patients) was estimated from the distribution of vPhenotye fold-changes across the cohort. The distribution of vPhenotypes from a large cohort of HIV patients who have failed therapy are presented for all available antiretroviral agents. A maximum change in IC₅₀ of at least 13-fold was observed for all drugs. The dideoxy drugs, tenofovir and most PIs exhibited small "dynamic ranges" with values of <4-fold change observed in > 99% of samples. In contrast, zidovudine, lamivudine, emtricitabine and the non-nucleoside reverse transcriptase inihibitors (excluding etravirine) had large dynamic ranges. We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner.