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

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.

Methods: 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.

Results: 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.

Conclusion: We describe the populational distribution of vPhenotypes such that vPhenotype results can be interpreted relative to other patients in a drug-specific manner.