Different selection patterns of resistance and cross-resistance to HIV-1 agents targeting CCR5.

Methods: Genotypic and phenotypic tests were used to evaluate the resistance of virus isolated from cell culture in the presence of the CCR5 inhibitor TAK-779.

Results: Mutations conferring resistance appeared in the gp120 sequence but were not confined to the V3 loop region, and both strains had a different mutation pattern. Recombination of the env gene of the BaL-derived resistant virus into the HIV-1 HXB2 wild-type backbone conferred resistance to TAK-779 and cross-resistance to maraviroc, with 63- and 11-fold changes in their EC(50) (50% effective concentration), respectively, together with an apparent reduction of the maximal plateau inhibition (MPI) of TAK-779 but not of maraviroc. Conversely, the resistant CI viruses showed an approximately 50% reduction in MPI for both TAK-779 and maraviroc.

Conclusion: Mutations conferring resistance appeared in the gp120 sequence but were not confined to the V3 loop region, and both strains had a different mutation pattern. Recombination of the env gene of the BaL-derived resistant virus into the HIV-1 HXB2 wild-type backbone conferred resistance to TAK-779 and cross-resistance to maraviroc, with 63- and 11-fold changes in their EC(50) (50% effective concentration), respectively, together with an apparent reduction of the maximal plateau inhibition (MPI) of TAK-779 but not of maraviroc. Conversely, the resistant CI viruses showed an approximately 50% reduction in MPI for both TAK-779 and maraviroc.