Association of antiretroviral resistance genotypes with response to therapy--comparison of three models

Marlynne Nicol, SDW Frost, S McDonagh, SM Burns, D Clutterbuck, A McMillan, CS Leen, AJ Leigh Brown

Research output: Contribution to journalArticlepeer-review

Abstract

Genotype-based resistance assays are commonly used to aid treatment in HIV-infected individuals failing antiretroviral therapy. The relationship between genotype and antiretroviral therapy comes mostly from in vitro assays of the response to a single drugs although there is a need for a prediction of clinical response to combination therapy. We have compared three different methods of analysing genotype data as a predictor of clinical response in a small clinical cohort of highly antiretroviral-experienced individuals failing therapy. No method performed well beyond 8 weeks into a new therapeutic regimen. A model based on the number of 'primary' mutations was statistically significant, but a multiple regression model, which identified specific mutations explained threefold more variation in response. Optimal prediction in this dataset was given by a model obtained from a classification tree analysis, in which genotype at amino acid sites 135 and 202 were combined with amino acid site 184, which explained over 50% of the deviance in the data and had a classification success of 86%.
Original languageEnglish
Pages (from-to)151-157
Number of pages7
JournalAntiviral Therapy
Volume7
Issue number3
Publication statusPublished - Oct 2002

Keywords

  • Adult
  • Amino Acid Sequence
  • Anti-HIV Agents
  • Drug Resistance, Viral
  • Female
  • Genetic Variation
  • Genotype
  • HIV
  • HIV Infections
  • HIV Protease
  • HIV Reverse Transcriptase
  • Humans
  • Male
  • Middle Aged
  • Models, Biological
  • Mutation
  • Phylogeny
  • Retrospective Studies

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