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

PLoS One. 2011 Feb 24;6(2):e17402. doi: 10.1371/journal.pone.0017402.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / therapeutic use*
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Resistance, Viral / drug effects
  • Drug Resistance, Viral / genetics*
  • Follow-Up Studies
  • Forecasting
  • Genotype
  • HIV Infections / diagnosis*
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Nonlinear Dynamics
  • Phenotype
  • Practice Patterns, Physicians'
  • Professional Practice
  • Prognosis
  • Treatment Failure
  • Viral Load / genetics

Substances

  • Anti-HIV Agents