Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
3396455 | Clinical Microbiology and Infection | 2015 | 6 Pages |
Abstract
We characterized maraviroc susceptibility of dual/mixed tropic viruses from subjects enrolled onto phase IIb study A4001029. Maraviroc baseline plasma samples from 13 multidrug-experienced subjects were sequenced and the HIV-1-env gene cloned into pNL4.3Îenv to obtain recombinant viruses. The V3 region was sequenced by the Sanger method and ultradeep sequencing. By analysing subjects having a weighted optimized background therapy susceptibility (wOBT) score of <1, 3/7 subjects were characterized by good in vivo and in vitro response to maraviroc therapy. Molecular docking simulations allowed us to rationalize the maraviroc susceptibility of dual/mixed tropic viruses. A subset of subjects with dual/mixed tropic viruses responded to maraviroc. Further investigations are warranted of CCR5 antagonists in subjects carrying dual/mixed tropic virus that explore the feasible use of maraviroc in subjects that is potentially larger than those infected with a pure R5 virus.
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Authors
M. Surdo, C. Alteri, M.C. Puertas, P. Saccomandi, L. Parrotta, L. Swenson, D. Chapman, G. Costa, A. Artese, E. Balestra, S. Aquaro, S. Alcaro, M. Lewis, B. Clotet, R. Harrigan, H. Valdez, V. Svicher, C.F. Perno, F. Ceccherini-Silberstein,