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

<h4>Background</h4>'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.<h4>Methods</h4>All HIV-in...

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Auteurs principaux: Luke C Swenson, Graham Pollock, Brian Wynhoven, Theresa Mo, Winnie Dong, Robert S Hogg, Julio S G Montaner, P Richard Harrigan
Format: article
Langue:EN
Publié: Public Library of Science (PLoS) 2011
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Accès en ligne:https://doaj.org/article/3059e66ab4d6446b86b08340fd903ccc
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Résumé:<h4>Background</h4>'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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner.