Low frequency of amino acid changes associated with resistance to attachment inhibitor BMS-626529 in R5- and X4-tropic HIV-1 B subtypes

• Published in: Antiviral therapy Vol. 18; p. A32
• Main Authors: Soulie, C, Ait-Arkoub, Z, Fofana, D B, Lambert-Niclot, S, Fourati, S, Sayon, S, Simon, A, Katlama, C, Raffi, F, Flandre, P, Calvez, V, Marcelin, A G
• Format: Journal Article
• Language: English
• Published: 01.01.2013
• Subjects: Human immunodeficiency virus 1
• ISSN: 1359-6535

BMS-626529 is a novel attachment inhibitor that targets HIV-1 gp120 and inhibits its binding to CD4+ T-cells. In the only in vivo study of BMS-626529 8 days monotherapy, administrated as its prodrug form to patients infected by HIV-1 B subtypes, env substitutions M426L and S375M were found to be strongly associated with low susceptibility to BMS-626529. M434I, S375T and M475I also contributed to loss of phenotypic susceptibility in some non-responders. Sequences of env gp120 from 109 patients infected by HIV-1 B subtypes and attachment inhibitor naive were analysed both for tropism and presence of previously described combinations of mutations linked to resistance to BMS-626529. The genotypic determination of tropism was realized using Geno2pheno algorithm with a false positive rate of 10%. A low prevalence of primary resistances to BMS-626529 was observed for this population of patients infected by HIV-1 B subtype. Furthermore, there was no difference of the mutation's distribution according to the virus tropism.