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

Effect of maraviroc on non-R5 tropic HIV-1: refined analysis of subjects from the phase IIb study A4001029
 
Surdo, M. ; Alteri, C. ; Puertas, M.C. ; Saccomandi, P. ; Parrotta, L. ; Swenson, L. ; Chapman, D. ; Costa, G. ; Artese, A. ; Balestra, E. ; Aquaro, S. ; Alcaro, S. ; Lewis, M. ; Clotet, Bonaventura ; Harrigan, R. ; Valdez, H. ; Svicher, V. ; Perno, C.F. ; Martinez Picado, Francisco Javier ; Ceccherini-Silberstein, Francesca
2015

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Nom: artconlli_a2015_surdo_m_effect_maraviroc.pdf
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Enllaç permanent: http://hdl.handle.net/10854/3997
 
Versió de l'editor: https://doi.org/10.1016/j.cmi.2014.08.002
 

Resum:

We characterized maraviroc susceptibility of dual/mixed tropic viruses from subjects enrolled onto phase IIb study A4001029. Maraviroc baseline plasma samples from 13 multidrugexperienced subjects were sequenced and the HIV-1-env gene cloned into pNL4.3Δenv to obtain recombinant viruses. The V3 region was sequenced by the ...»»»»
We characterized maraviroc susceptibility of dual/mixed tropic viruses from subjects enrolled onto phase IIb study A4001029. Maraviroc baseline plasma samples from 13 multidrugexperienced 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.^^^^

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(c) Wiley
 

Citació Bibliogràfica:

Surdo, M., Alteri, C., Puertas, M. C., 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.