HIV type 1 genetic diversity is a major obstacle for antiretroviral drug resistance hybridization-based assays

Human immunodeficiency virus type 1 (HIV-1) is characterized by high geneti c diversity. Current antiretroviral (ARV) drug resistance genotyping assays have been designed on the basis of the most prevalent sequence patterns ci rculating in the United States and Europe, which belong to the B subtype. H owever, little is known about their performance on non-B subtype samples. I n 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 ass ay. Samples taken from 93 HIV-1-infected individuals of Buenos Aires, Argen tina were studied. The reverse transcriptase (RT) region of HIV-1 was genot ypically assessed by a line probe assay (INNO-LiPA HIV-1 RT; Innogenetics, Ghent, Belgium) and automatic sequencing (TruGene and OpenGene; Visible Gen etics, Toronto, Canada). Phylogenetic and intersubtype recombination analys es were carried out, showing that 52 of 93 (55.9%) samples belonged to subt ype B, whereas 41 of 93 (44.1%) showed a (59) 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 sample s showed a nonreacting result, indicating a significant difference in the s ubtype distribution of the nonreacting samples. The presence of a synonymou s 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 recombinan t samples (p < 0.001). The present data indicate that HIV-1 genetic diversi ty is a major obstacle for ARV drug resistance hybridization-based assays.