title: Discordances between interpretation algorithms for genotypic resistance to protease and reverse transcriptase inhibitors of human immunodeficiency virus are subtype dependent.
abstract: The major limitation of drug resistance genotyping for human immunodeficiency virus remains the interpretation of the results. We evaluated the concordance in predicting therapy response between four different interpretation algorithms (Rega 6.3, HIVDB-08/04, ANRS [07/04], and VGI 8.0). Sequences were gathered through a worldwide effort to establish a database of non-B subtype sequences, and demographic and clinical information about the patients was gathered. The most concordant results were found for nonnucleoside reverse transcriptase (RT) inhibitors (93%), followed by protease inhibitors (84%) and nucleoside RT inhibitor (NRTIs) (76%). For therapy-naive patients, for nelfinavir, especially for subtypes C and G, the discordances were driven mainly by the protease (PRO) mutational pattern 82I/V + 63P + 36I/V for subtype C and 82I + 63P + 36I + 20I for subtype G. Subtype F displayed more discordances for ritonavir in untreated patients due to the combined presence of PRO 20R and 10I/V. In therapy-experienced patients, subtype G displayed a lot of discordances for saquinavir and indinavir due to mutational patterns involving PRO 90 M and 82I. Subtype F had more discordance for nelfinavir attributable to the presence of PRO 88S and 82A + 54V. For the NRTIs lamivudine and emtricitabine, CRF01_AE had more discordances than subtype B due to the presence of RT mutational patterns 65R + 115 M and 118I + 215Y, respectively. Overall, the different algorithms agreed well on the level of resistance scored, but some of the discordances could be attributed to specific (subtype-dependent) combinations of mutations. It is not yet known whether therapy response is subtype dependent, but the advice given to clinicians based on a genotypic interpretation algorithm differs according to the subtype.
authors.affiliation: Rega Institute for Medical Research, Minderbroedersstraat 10, 3000 Leuven, Belgium.
authors.forename: Joke
authors.initials: J
authors.lastname: Snoeck
authors.forename: Rami
authors.initials: R
authors.lastname: Kantor
authors.forename: Robert W
authors.initials: RW
authors.lastname: Shafer
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Laethem
authors.forename: Koen
authors.initials: K
authors.lastname: Deforche
authors.forename: Ana Patricia
authors.initials: AP
authors.lastname: Carvalho
authors.forename: Brian
authors.initials: B
authors.lastname: Wynhoven
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Soares
authors.forename: Patricia
authors.initials: P
authors.lastname: Cane
authors.forename: John
authors.initials: J
authors.lastname: Clarke
authors.forename: Candice
authors.initials: C
authors.lastname: Pillay
authors.forename: Sunee
authors.initials: S
authors.lastname: Sirivichayakul
authors.forename: Koya
authors.initials: K
authors.lastname: Ariyoshi
authors.forename: Africa
authors.initials: A
authors.lastname: Holguin
authors.forename: Hagit
authors.initials: H
authors.lastname: Rudich
authors.forename: Rosangela
authors.initials: R
authors.lastname: Rodrigues
authors.forename: Maria Belen
authors.initials: MB
authors.lastname: Bouzas
authors.forename: Françoise
authors.initials: F
authors.lastname: Brun-Vézinet
authors.forename: Caroline
authors.initials: C
authors.lastname: Reid
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Brigido
authors.forename: Zehava
authors.initials: Z
authors.lastname: Grossman
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Wataru
authors.initials: W
authors.lastname: Sugiura
authors.forename: Praphan
authors.initials: P
authors.lastname: Phanuphak
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weber
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
authors.forename: Richard P
authors.initials: RP
authors.lastname: Harrigan
authors.forename: Ricardo
authors.initials: R
authors.lastname: Camacho
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schapiro
authors.forename: David
authors.initials: D
authors.lastname: Katzenstein
authors.forename: Anne-Mieke
authors.initials: AM
authors.lastname: Vandamme
mesh_terms: D000465:Algorithms; D024882:Drug Resistance, Viral; D005838:Genotype; D006678:HIV / Q000145:classification / Q000187:drug effects* / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
chemical_list: D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors