Mutations in human immunodeficiency virus type 1 integrase confer resistance to the naphthyridine L-870,810 and cross-resistance to the clinical trial drug GS-9137.

ABSTRACT: To gain further insight into the understanding of the antiviral resistance patterns and mechanisms of the integrase strand transfer inhibitor L-870,810, the prototypical naphthyridine analogue, we passaged the human immunodeficiency virus type 1 strain HIV-1(III(B)) in cell culture in the presence of increasing concentrations of L-870,810 (III(B)/L-870,810). The mutations L74M, E92Q, and S230N were successively selected in the integrase. The L74M and E92Q mutations have both been associated in the past with resistance against the diketo acid (DKA) analogues L-708,906 and S-1360 and the clinical trial drugs MK-0518 and GS-9137. After 20, 40, and 60 passages in the presence of L-870,810, III(B)/L-870,810 displayed 22-, 34-, and 110-fold reduced susceptibility to L-870,810, respectively. Phen

SUBMITTER: Hombrouck A 

PROVIDER: S-EPMC2415791 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature