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

TitleInitiatives for developing and comparing genotype interpretation systems: external validation of existing rule-based interpretation systems for abacavir against virological response
Publication TypeJournal Article
Year of Publication2008
AuthorsCozzi-Lepri A
JournalHIV Med
Volume9
Pagination27-40
Date PublishedJan
ISBN Number1464-2662 (Print)<br/>1464-2662
Accession Number18199170
Keywords*Genotype, Adult, Anti-HIV Agents/*therapeutic use, Dideoxynucleosides/*therapeutic use, Drug Resistance, Viral/*genetics, Female, HIV Infections/drug therapy/*genetics, HIV-1/*drug effects/genetics, Humans, Male, Middle Aged, RNA, Viral/blood, Viral Load
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.

Short TitleHIV medicine
Alternate JournalHIV medicine