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

Cozzi-Lepri A,

Royal Free and University College Medical School, University College London, London, UK.

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.

Published 17 January 2008 in HIV Med, 9(1): 27-40.
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