“Dynamic Range” of Inferred Phenotypic HIV Drug Resistance Values in Clinical Practice

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Background‘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.MethodsAll 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.ResultsThe 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.ConclusionWe describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner.
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Swenson LC, Pollock G, Wynhoven B, Mo T, Dong W, et al. (2011) “Dynamic Range” of Inferred Phenotypic HIV Drug Resistance Values in Clinical Practice. PLoS ONE 6(2): e17402. doi:10.1371/journal.pone.0017402
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“Dynamic Range” of Inferred Phenotypic HIV Drug Resistance Values in Clinical Practice
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