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

M. Surdo, C. Alteri, M. C. 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. F. Perno, J. Martinez-Picado, F. Ceccherini-Silberstein

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Abstract

© 2014 European Society of Clinical Microbiology and Infectious Diseases. 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 invivo and invitro 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.
Original languageEnglish
Pages (from-to)103.e1-103.e6
JournalClinical Microbiology and Infection
Volume21
Issue number1
DOIs
Publication statusPublished - 1 Jan 2015

Keywords

  • Dual/mixed virus
  • HIV
  • Maraviroc
  • Phenotypic activity
  • UDPS

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    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. (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. https://doi.org/10.1016/j.cmi.2014.08.002