Effect of maraviroc on non-R5 tropic HIV-1: refined analysis of subjects from the phase IIb study A4001029
Articolo
Data di Pubblicazione:
2015
Citazione:
Effect of maraviroc on non-R5 tropic HIV-1: refined analysis of subjects from the phase IIb study A4001029 / M. Surdo, C. Alteri, M. 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. Perno, J. Martinez-Picado, F. Ceccherini-Silberstein. - In: CLINICAL MICROBIOLOGY AND INFECTION. - ISSN 1198-743X. - 21:1(2015 Jan), pp. 103.e1-103.e6. [10.1016/j.cmi.2014.08.002]
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 pNL4.3Δenv 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Dual/mixed virus; HIV; UDPS; maraviroc; phenotypic activity
Elenco autori:
M. Surdo, C. Alteri, M. 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. Perno, J. Martinez-Picado, F. Ceccherini-Silberstein
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