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

doi: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

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

Department of Medicine

Research output: Contribution to journal › Article › Research › peer-review

5 Citations (Scopus)

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 language	English
Pages (from-to)	103.e1-103.e6
Journal	Clinical Microbiology and Infection
Volume	21
Issue number	1
DOIs	https://doi.org/10.1016/j.cmi.2014.08.002
Publication status	Published - 1 Jan 2015

Keywords

Dual/mixed virus
HIV
Maraviroc
Phenotypic activity
UDPS

UN SDGs

This output contributes to the following Sustainable Development Goal(s)

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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

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. / Effect of maraviroc on non-R5 tropic HIV-1: Refined analysis of subjects from the phase IIb study A4001029. In: Clinical Microbiology and Infection. 2015 ; Vol. 21, No. 1. pp. 103.e1-103.e6.

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abstract = "{\textcopyright} 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.",

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author = "M. Surdo and C. Alteri and Puertas, {M. C.} and P. Saccomandi and L. Parrotta and L. Swenson and D. Chapman and G. Costa and A. Artese and E. Balestra and S. Aquaro and S. Alcaro and M. Lewis and B. Clotet and R. Harrigan and H. Valdez and V. Svicher and Perno, {C. F.} and J. Martinez-Picado and F. Ceccherini-Silberstein",

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Surdo, M, Alteri, C, Puertas, MC, 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 2015, 'Effect of maraviroc on non-R5 tropic HIV-1: Refined analysis of subjects from the phase IIb study A4001029', Clinical Microbiology and Infection, vol. 21, no. 1, pp. 103.e1-103.e6. https://doi.org/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. / 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.

In: Clinical Microbiology and Infection, Vol. 21, No. 1, 01.01.2015, p. 103.e1-103.e6.

Research output: Contribution to journal › Article › Research › peer-review

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AU - Surdo, M.

AU - Alteri, C.

AU - Puertas, M. C.

AU - Saccomandi, P.

AU - Parrotta, L.

AU - Swenson, L.

AU - Chapman, D.

AU - Costa, G.

AU - Artese, A.

AU - Balestra, E.

AU - Aquaro, S.

AU - Alcaro, S.

AU - Lewis, M.

AU - Clotet, B.

AU - Harrigan, R.

AU - Valdez, H.

AU - Svicher, V.

AU - Perno, C. F.

AU - Martinez-Picado, J.

AU - Ceccherini-Silberstein, F.

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N2 - © 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.

AB - © 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.

KW - Dual/mixed virus

KW - HIV

KW - Maraviroc

KW - Phenotypic activity

KW - UDPS

U2 - 10.1016/j.cmi.2014.08.002

DO - 10.1016/j.cmi.2014.08.002

M3 - Article

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