title: HIV-1 protease and reverse transcriptase mutation patterns responsible for discordances between genotypic drug resistance interpretation algorithms.
abstract: Several rules-based algorithms have been developed to interpret results of HIV-1 genotypic resistance tests. To assess the concordance of these algorithms and to identify sequences causing interalgorithm discordances, we applied four publicly available algorithms to the sequences of isolates from 2,045 individuals in northern California. Drug resistance interpretations were classified as S for susceptible, I for intermediate, and R for resistant. Of 30,675 interpretations (2,045 sequences x 15 drugs), 4.4% were completely discordant, with at least one algorithm assigning an S and another an R; 29.2% were partially discordant, with at least one algorithm assigning an S and another an I, or at least one algorithm assigning an I and another an R; and 66.4% displayed complete concordance, with all four algorithms assigning the same interpretation. Discordances between nucleoside reverse transcriptase inhibitor interpretations usually resulted from several simple, frequently occurring mutational patterns. Discordances between protease inhibitor interpretations resulted from a larger number of more complex mutation patterns. Discordances between nonnucleoside reverse transcriptase inhibitor interpretations were uncommon and resulted from a small number of individual drug resistance mutations. Determining the clinical significance of these mutation patterns responsible for interalgorithm discordances will improve interalgorithm concordance and the accuracy of genotypic resistance interpretation.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, California 94301, USA.
authors.forename: Jaideep
authors.initials: J
authors.lastname: Ravela
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Betts
authors.forename: Francoise
authors.initials: F
authors.lastname: Brun-Vézinet
authors.forename: Anne-Mieke
authors.initials: AM
authors.lastname: Vandamme
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.forename: Kristel
authors.initials: K
authors.lastname: van Laethem
authors.forename: Kate
authors.initials: K
authors.lastname: Smith
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schapiro
authors.forename: Dean L
authors.initials: DL
authors.lastname: Winslow
authors.forename: Caroline
authors.initials: C
authors.lastname: Reid
authors.forename: Robert W
authors.initials: RW
authors.lastname: Shafer
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D054303:HIV Reverse Transcriptase; D016333:HIV Protease