title: HIV type 1 genetic diversity is a major obstacle for antiretroviral drug resistance hybridization-based assays.
abstract: Human immunodeficiency virus type 1 (HIV-1) is characterized by high genetic diversity. Current antiretroviral (ARV) drug resistance genotyping assays have been designed on the basis of the most prevalent sequence patterns circulating in the United States and Europe, which belong to the B subtype. However, little is known about their performance on non-B subtype samples. In Argentina, circulating forms have been characterized as subtypes B, C, F, and B/F recombinant forms. Our aim was to analyze the association between the genetic diversity of HIV-1 forms circulating in Argentina and the lack of reactivity at codon 74 in an ARV drug resistance hybridization-based assay. Samples taken from 93 HIV-1-infected individuals of Buenos Aires, Argentina were studied. The reverse transcriptase (RT) region of HIV-1 was genotypically assessed by a line probe assay (INNO-LiPA HIV-1 RT; Innogenetics, Ghent, Belgium) and automatic sequencing (TruGene and OpenGene; Visible Genetics, Toronto, Canada). Phylogenetic and intersubtype recombination analyses were carried out, showing that 52 of 93 (55.9%) samples belonged to subtype B, whereas 41 of 93 (44.1%) showed a (5') F1/B (3') subtype recombinant genomic structure. For codon 74 in the LiPA test, 4 of 52 (7.7%) B-subtype samples were nonreactive, whereas 27 of 41 (65.9 %) F1/B recombinant samples showed a nonreacting result, indicating a significant difference in the subtype distribution of the nonreacting samples. The presence of a synonymous polymorphism at codon 72 of RT (AGA --> AGG) associated with the lack of reaction at codon 74 in LiPA, was more prevalent in F1/B subtype recombinant samples (p < 0.001). The present data indicate that HIV-1 genetic diversity is a major obstacle for ARV drug resistance hybridization-based assays.
authors.affiliation: National Reference Center for AIDS, Department of Microbiology, School of Medicine, University of Buenos Aires, 1121 Buenos Aires, Argentina.
authors.forename: G H
authors.initials: GH
authors.lastname: Kijak
authors.forename: A E
authors.initials: AE
authors.lastname: Rubio
authors.forename: J F
authors.initials: JF
authors.lastname: Quarleri
authors.forename: H
authors.initials: H
authors.lastname: Salomón
mesh_terms: D001483:Base Sequence; D004279:DNA, Viral; D024882:Drug Resistance, Viral / Q000235:genetics*; D014644:Genetic Variation; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization / Q000379:methods; D010802:Phylogeny; D011995:Recombination, Genetic
chemical_list: D004279:DNA, Viral; D054303:HIV Reverse Transcriptase