Effect of maraviroc on non-R5 tropic HIV-1: refined analysis of subjects from the phase IIb study A4001029. (January 2015)

• Record Type: Journal Article
• Authors: 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, B.; Harrigan, R.; Valdez, H.; Svicher, V.; Perno, C.F.; Martinez-Picado, J.; Ceccherini-Silberstein, F.
• Is Part Of: Clinical microbiology and infection. Volume 21:Number 1(2015:Jan.)
• Page Start: 103.e1
• Page End: 103.e6
• Publication Date: 2015-01
• Subjects: Dual/mixed virus -- HIV -- maraviroc -- phenotypic activity -- UDPS; Medical microbiology -- Periodicals; Diagnostic microbiology -- Periodicals; Communicable diseases -- Periodicals; Infection -- Periodicals; 616.01
• DOI: 10.1016/j.cmi.2014.08.002
• Languages: English
• ISSNs: 1198-743X

Abstract

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.