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.

Surdo, M., Alteri, C., Puertas, M., Saccomandi, P., Parrotta, L., Swenson, L., et al. (2015). Effect of maraviroc on non-R5 tropic HIV-1: Refined analysis of subjects from the phase IIb study A4001029. CLINICAL MICROBIOLOGY AND INFECTION, 21(1), 103.e1-103.e6 [10.1016/j.cmi.2014.08.002].

Effect of maraviroc on non-R5 tropic HIV-1: Refined analysis of subjects from the phase IIb study A4001029

ALTERI, CLAUDIA;SACCOMANDI, PATRIZIA;ARTESE, ANNA;BALESTRA, EMANUELA;AQUARO, STEFANO;SVICHER, VALENTINA;PERNO, CARLO FEDERICO;CECCHERINI SILBERSTEIN, FRANCESCA
2015-01-01

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.
gen-2015
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Dual/mixed virus; HIV; UDPS; maraviroc; phenotypic activity
Surdo, M., Alteri, C., Puertas, M., Saccomandi, P., Parrotta, L., Swenson, L., et al. (2015). Effect of maraviroc on non-R5 tropic HIV-1: Refined analysis of subjects from the phase IIb study A4001029. CLINICAL MICROBIOLOGY AND INFECTION, 21(1), 103.e1-103.e6 [10.1016/j.cmi.2014.08.002].
Surdo, M; Alteri, C; Puertas, M; Saccomandi, P; Parrotta, L; Swenson, L; Chapman, D; Costa, G; Artese, A; Balestra, E; Aquaro, S; Alcaro, S; Lewis, M; Clotet, B; Harrigan, R; Valdez, H; Svicher, V; Perno, Cf; Martinez Picado, J; CECCHERINI SILBERSTEIN, F
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/113126
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