title: Effect of maraviroc on non-R5 tropic HIV-1: refined analysis of subjects from the phase IIb study A4001029.
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.
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: M
authors: M
authors: Surdo
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: C
authors: C
authors: Alteri
authors: Institut de Recerca de la SIDA irsiCaixa, Hospital Universitari 'Germans Trias i Pujol', Badalona, Universitat Autònoma de Barcelona (UAB), Catalonia, Spain.
authors: M C
authors: MC
authors: Puertas
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: P
authors: P
authors: Saccomandi
authors: Department of Pharmacobiological Sciences, University of Catanzaro 'Magna Græcia', Catanzaro, Italy.
authors: L
authors: L
authors: Parrotta
authors: BC Centre for Excellence in HIV/AIDS, Vancouver, Canada.
authors: L
authors: L
authors: Swenson
authors: Pfizer, New York, NY, USA.
authors: D
authors: D
authors: Chapman
authors: Department of Pharmacobiological Sciences, University of Catanzaro 'Magna Græcia', Catanzaro, Italy.
authors: G
authors: G
authors: Costa
authors: Department of Pharmacobiological Sciences, University of Catanzaro 'Magna Græcia', Catanzaro, Italy.
authors: A
authors: A
authors: Artese
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: E
authors: E
authors: Balestra
authors: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
authors: S
authors: S
authors: Aquaro
authors: Department of Pharmacobiological Sciences, University of Catanzaro 'Magna Græcia', Catanzaro, Italy.
authors: S
authors: S
authors: Alcaro
authors: Pfizer, UK.
authors: M
authors: M
authors: Lewis
authors: Institut de Recerca de la SIDA irsiCaixa, Hospital Universitari 'Germans Trias i Pujol', Badalona, Universitat Autònoma de Barcelona (UAB), Catalonia, Spain; Universitat de Vic (UVic), Catalonia, Spain.
authors: B
authors: B
authors: Clotet
authors: BC Centre for Excellence in HIV/AIDS, Vancouver, Canada.
authors: R
authors: R
authors: Harrigan
authors: Pfizer, New York, NY, USA.
authors: H
authors: H
authors: Valdez
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: V
authors: V
authors: Svicher
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.
authors: C F
authors: CF
authors: Perno
authors: Institut de Recerca de la SIDA irsiCaixa, Hospital Universitari 'Germans Trias i Pujol', Badalona, Universitat Autònoma de Barcelona (UAB), Catalonia, Spain; Universitat de Vic (UVic), Catalonia, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors: J
authors: J
authors: Martinez-Picado
authors: Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy. Electronic address: ceccherini@med.uniroma2.it.
authors: F
authors: F
authors: Ceccherini-Silberstein
mesh_terms: D065100:CCR5 Receptor Antagonists / Q000494:pharmacology*; D003510:Cyclohexanes / Q000494:pharmacology*; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D000077592:Maraviroc; D009154:Mutation / Q000235:genetics; D014230:Triazoles / Q000494:pharmacology*; D056189:Viral Tropism
chemical_list: D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc
keywords: Dual/mixed virus; HIV; UDPS; maraviroc; phenotypic activity