Association of antiretroviral resistance genotypes with response to therapy--comparison of three models.
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%.
Quigg
Marlynne
M
Centre for HIV Research, Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh, UK.
Frost
Simon D W
SD
McDonagh
Susan
S
Burns
Sheila M
SM
Clutterbuck
Daniel
D
McMillan
Alexander
A
Leen
Clifford S
CS
Brown
Andrew J Leigh
AJ
D000328:Adult; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D016333:HIV Protease / Q000737:chemistry / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation; D010802:Phylogeny; D012189:Retrospective Studies
D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase; D016333:HIV Protease