Initiatives for developing and comparing genotype interpretation systems: external validation of existing rule-based interpretation systems for abacavir against virological response

HIV Med. 2008 Jan;9(1):27-40. doi: 10.1111/j.1468-1293.2008.00523.x.

Abstract

Objectives: To investigate the concordance between any of the results of nine HIV-1 drug-resistance interpretation systems (ISs) and their ability to predict week 8 and week 24 virological responses to abacavir-containing combination therapy.

Patients and methods: A total of 1306 HIV-infected patients with a viral load >500 HIV-1 RNA copies/mL and a baseline genotypic resistance test were included in the study. Predicted abacavir susceptibilities according to each rule-based IS were compared. Linear and logistic regressions were used to assess the prognostic value of each IS for week 8 and week 24 responses, respectively.

Results: A median of three (interquartile range 1-5) abacavir mutations were detected at baseline. Comparing the IS predictions for abacavir susceptibility, 9% to 45% of patients were predicted to have resistant (R) virus, 9% to 53% virus with intermediate (I) resistance, and 23% to 74% susceptible (S) virus. Overall, the median week 8 viral load reduction was 1.61 log(10) copies/mL (95% confidence interval 1.52-1.71) and 50% of patients experienced virological failure at 24 weeks. Most ISs showed better virological responses with S and I viruses than with R viruses.

Conclusions: Despite some degree of variability in predicted abacavir susceptibility among ISs, most ISs are useful to predict virological response.

Publication types

  • Research Support, N.I.H., Extramural
  • Validation Study

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Dideoxynucleosides / therapeutic use*
  • Drug Resistance, Viral / genetics*
  • Female
  • Genotype*
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Viral Load

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • RNA, Viral
  • abacavir