Comparison between rules-based human immunodeficiency virus type 1 genotype interpretations and real or virtual phenotype: Concordance analysis and correlation with clinical outcome in heavily treated patients

We compared 2 rules-based genotype interpretation systems and real or virtual phenotype through a retrospective analysis of a prospective trial. Genotypes were determined with VircoGEN II (VIRCO) and were interpreted with either RetroGram 1.4 or TRUGENE HIV-1 ( guidelines 3.0) or original virtual phenotype ( Virtual Phenotype; VIRCO), as available in the year 2000. Among 188 human immunodeficiency virus (HIV) type 1 isolates, overall concordance (kappa agreement) was observed for the 2 rules-based systems, whereas striking discordances were noted between them and real and virtual phenotype interpretations for stavudine, didanosine, zalcitabine, abacavir, and amprenavir (kappa<0.4). Clinical evaluation of a subset of 173 patients showed that both rules- based sensitivity scores were independently associated with HIV RNA loads < 400 copies/ mL at week 16 of during-treatment analysis (TRUGENE: odds ratio [OR], 2.90; 95% confidence interval [CI], 1.52 - 5.52; P = .001; RetroGram: OR, 2.34; 95% CI, 1.21 - 4.55; P = .012), whereas, in contrast to real or virtual phenotype, interpretations according to biological cut-offs were not (OR, 1.91; 95% CI, 0.77 - 4.76; P = .162).