Initiatives for developing and comparing genotype interpretation systems: External validation of existing systems for didanosine against virological response JOURNAL OF INFECTIOUS DISEASES Assoumou, L., Brun-Vezinet, F., Cozzi-Lepri, A., Kuritzkes, D., Phillips, A., Zolopa, A., DeGruttola, V., Miller, V., Costagliola, D. 2008; 198 (4): 470-480

Abstract

This study was performed to investigate the concordance between commonly used human immunodeficiency virus type 1 (HIV-1) drug resistance interpretation systems for didanosine (ddI) and their ability to predict responses at weeks 8 and 24.The study included drug-experienced HIV-infected patients who had viral loads >500 copies/mL and who underwent a genotypic resistance test when beginning a ddI-containing therapy. The interpretations of the level of resistance to ddI were compared for the 6 interpretation systems. Linear and logistic regression were used to assess their ability to predict responses for weeks 8 and 24, respectively.The 1453 patients had a median viral load of 4.3 log10 copies/mL, and 31% were preexposed to ddI. Complete concordance was found for 19% of samples, partial discordance for 49%, and complete discordance for 32%. The median viral load reduction at week 8 was 1.36 log10 copies/mL, and 56% of patients had viral loads > 400 copies/mL at week 24. At week 8, all systems correctly predicted a greater viral load reduction in patients with susceptible viruses than in those with resistant viruses, but only the Stanford system was able to discriminate between patients with resistant, intermediately resistant, and susceptible viruses. No systems predicted virological response correctly at week 24.Our results show the need for standardized methods to establish genotypic interpretation systems.

View details for DOI 10.1086/590156

View details for Web of Science ID 000257893300004

View details for PubMedID 18598191