Using drug exposure for predicting drug resistance - A data-driven genotypic interpretation tool

PLoS One. 2017 Apr 10;12(4):e0174992. doi: 10.1371/journal.pone.0174992. eCollection 2017.

Abstract

Antiretroviral treatment history and past HIV-1 genotypes have been shown to be useful predictors for the success of antiretroviral therapy. However, this information may be unavailable or inaccurate, particularly for patients with multiple treatment lines often attending different clinics. We trained statistical models for predicting drug exposure from current HIV-1 genotype. These models were trained on 63,742 HIV-1 nucleotide sequences derived from patients with known therapeutic history, and on 6,836 genotype-phenotype pairs (GPPs). The mean performance regarding prediction of drug exposure on two test sets was 0.78 and 0.76 (ROC-AUC), respectively. The mean correlation to phenotypic resistance in GPPs was 0.51 (PhenoSense) and 0.46 (Antivirogram). Performance on prediction of therapy-success on two test sets based on genetic susceptibility scores was 0.71 and 0.63 (ROC-AUC), respectively. Compared to geno2pheno[resistance], our novel models display a similar or superior performance. Our models are freely available on the internet via www.geno2pheno.org. They can be used for inferring which drug compounds have previously been used by an HIV-1-infected patient, for predicting drug resistance, and for selecting an optimal antiretroviral therapy. Our data-driven models can be periodically retrained without expert intervention as clinical HIV-1 databases are updated and therefore reduce our dependency on hard-to-obtain GPPs.

MeSH terms

  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Area Under Curve
  • Databases, Factual
  • Drug Resistance, Viral / drug effects*
  • Genotype
  • HIV Infections / drug therapy
  • HIV-1 / genetics*
  • Humans
  • Internet
  • Models, Biological*
  • Models, Statistical
  • Phenotype
  • ROC Curve

Substances

  • Anti-HIV Agents

Grants and funding

This work was supported by Bundesministerium für Gesundheit, HIV-HEP-MASTER (IIA5-2013-2514AUK375). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.