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


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.
Cozzi-Lepri
A
A
Department of Primary Care and Population Sciences, Royal Free and University College Medical School, University College London, London, UK. a.cozzi-lepri@pcps.ucl.ac.uk
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D012367:RNA, Viral; D000099227:Abacavir