Reliable genotypic tropism tests for the major HIV-1 subtypes

Kieran Cashin; Lachlan R. Gray; Katherine L. Harvey; Danielle Perez-Bercoff; Guinevere Q. Lee; Jasminka Sterjovski; Michael Roche; James F. Demarest; Fraser Drummond; P. Richard Harrigan; Melissa J. Churchill; Paul R. Gorry

doi:10.1038/srep08543

Reliable genotypic tropism tests for the major HIV-1 subtypes

Kieran Cashin, Lachlan R. Gray, Katherine L. Harvey, Danielle Perez-Bercoff, Guinevere Q. Lee, Jasminka Sterjovski, Michael Roche, James F. Demarest, Fraser Drummond, P. Richard Harrigan, Melissa J. Churchill, Paul R. Gorry^*

^*Corresponding author for this work

Immuno-Pharmacology and Interactomics

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

36 Citations (Scopus)

Abstract

Over the past decade antiretroviral drugs have dramatically improved the prognosis for HIV-1 infected individuals, yet achieving better access to vulnerable populations remains a challenge. The principal obstacle to the CCR5-antagonist, maraviroc, from being more widely used in anti-HIV-1 therapy regimens is that the pre-treatment genotypic œ tropism tests to determine virus susceptibility to maraviroc have been developed primarily for HIV-1 subtype B strains, which account for only 10% of infections worldwide. We therefore developed PhenoSeq, a suite of HIV-1 genotypic tropism assays that are highly sensitive and specific for establishing the tropism of HIV-1 subtypes A, B, C, D and circulating recombinant forms of subtypes AE and AG, which together account for 95% of HIV-1 infections worldwide. The PhenoSeq platform will inform the appropriate use of maraviroc and future CCR5 blocking drugs in regions of the world where non-B HIV-1 predominates, which are burdened the most by the HIV-1 pandemic.

Original language	English
Article number	8543
Journal	Scientific Reports
Volume	5
DOIs	https://doi.org/10.1038/srep08543
Publication status	Published - 2015

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@article{d0eb7c07de9e44c398a189b20f22d748,

title = "Reliable genotypic tropism tests for the major HIV-1 subtypes",

abstract = "Over the past decade antiretroviral drugs have dramatically improved the prognosis for HIV-1 infected individuals, yet achieving better access to vulnerable populations remains a challenge. The principal obstacle to the CCR5-antagonist, maraviroc, from being more widely used in anti-HIV-1 therapy regimens is that the pre-treatment genotypic {\oe} tropism tests to determine virus susceptibility to maraviroc have been developed primarily for HIV-1 subtype B strains, which account for only 10% of infections worldwide. We therefore developed PhenoSeq, a suite of HIV-1 genotypic tropism assays that are highly sensitive and specific for establishing the tropism of HIV-1 subtypes A, B, C, D and circulating recombinant forms of subtypes AE and AG, which together account for 95% of HIV-1 infections worldwide. The PhenoSeq platform will inform the appropriate use of maraviroc and future CCR5 blocking drugs in regions of the world where non-B HIV-1 predominates, which are burdened the most by the HIV-1 pandemic.",

author = "Kieran Cashin and Gray, {Lachlan R.} and Harvey, {Katherine L.} and Danielle Perez-Bercoff and Lee, {Guinevere Q.} and Jasminka Sterjovski and Michael Roche and Demarest, {James F.} and Fraser Drummond and Harrigan, {P. Richard} and Churchill, {Melissa J.} and Gorry, {Paul R.}",

note = "Funding Information: We thank Rohan Gray for assistance with writing the code for the PhenoSeq algorithms and the bulk2clonal software, and Brendan Crabb for helpful comments. This study was supported by grants from (i) the Australian National Health and Medical Research Council (NHMRC) to P.R.G. and M.J.C. (1022066), (ii) the National Institutes of Health (NIH) to P.R.G. and M.J.C. (R21 MH100594), and (iii) the Delaney AIDS Research Enterprise (DARE) to M.J.C. and L.R.G. (U19 AI096109). K.Y.C. and K.L.H. are supported by Australian Postgraduate Awards from the University of Melbourne. P.R.G. is supported by an Australian Research Council (ARC) Future Fellowship (FT2). L.R.G. was supported by an Australian NHMRC Postdoctoral Training Fellowship. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute. Funding Information: Supplementary information accompanies this paper at http://www.nature.com/ scientificreports Competing financial interests: JFD and FD are employees of ViiV Healthcare. PRG is a former member of the ViiV Australia scientific advisory board and has received honoraria. KC and PRG have received honoraria from ViiV Healthcare Australia for conference travel. PRH is supported by CIHR/GSK Research Chair in Clinical Virology and has consulted and/or received grant funding from a variety pharmaceutical diagnostic companies and has received grants from, served as an ad hoc advisor to, or spoke at various events sponsored by: Pfizer, Glaxo-Smith Kline, Abbott, Merck, Selah, Tobira, Virco and Quest Diagnostics. None of the other authors have any competing interests to declare.",

year = "2015",

doi = "10.1038/srep08543",

language = "English",

volume = "5",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

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T1 - Reliable genotypic tropism tests for the major HIV-1 subtypes

AU - Cashin, Kieran

AU - Gray, Lachlan R.

AU - Harvey, Katherine L.

AU - Perez-Bercoff, Danielle

AU - Lee, Guinevere Q.

AU - Sterjovski, Jasminka

AU - Roche, Michael

AU - Demarest, James F.

AU - Drummond, Fraser

AU - Harrigan, P. Richard

AU - Churchill, Melissa J.

AU - Gorry, Paul R.

N1 - Funding Information: We thank Rohan Gray for assistance with writing the code for the PhenoSeq algorithms and the bulk2clonal software, and Brendan Crabb for helpful comments. This study was supported by grants from (i) the Australian National Health and Medical Research Council (NHMRC) to P.R.G. and M.J.C. (1022066), (ii) the National Institutes of Health (NIH) to P.R.G. and M.J.C. (R21 MH100594), and (iii) the Delaney AIDS Research Enterprise (DARE) to M.J.C. and L.R.G. (U19 AI096109). K.Y.C. and K.L.H. are supported by Australian Postgraduate Awards from the University of Melbourne. P.R.G. is supported by an Australian Research Council (ARC) Future Fellowship (FT2). L.R.G. was supported by an Australian NHMRC Postdoctoral Training Fellowship. The authors gratefully acknowledge the contribution to this work of the Victorian Operational Infrastructure Support Program received by the Burnet Institute. Funding Information: Supplementary information accompanies this paper at http://www.nature.com/ scientificreports Competing financial interests: JFD and FD are employees of ViiV Healthcare. PRG is a former member of the ViiV Australia scientific advisory board and has received honoraria. KC and PRG have received honoraria from ViiV Healthcare Australia for conference travel. PRH is supported by CIHR/GSK Research Chair in Clinical Virology and has consulted and/or received grant funding from a variety pharmaceutical diagnostic companies and has received grants from, served as an ad hoc advisor to, or spoke at various events sponsored by: Pfizer, Glaxo-Smith Kline, Abbott, Merck, Selah, Tobira, Virco and Quest Diagnostics. None of the other authors have any competing interests to declare.

PY - 2015

Y1 - 2015

N2 - Over the past decade antiretroviral drugs have dramatically improved the prognosis for HIV-1 infected individuals, yet achieving better access to vulnerable populations remains a challenge. The principal obstacle to the CCR5-antagonist, maraviroc, from being more widely used in anti-HIV-1 therapy regimens is that the pre-treatment genotypic œ tropism tests to determine virus susceptibility to maraviroc have been developed primarily for HIV-1 subtype B strains, which account for only 10% of infections worldwide. We therefore developed PhenoSeq, a suite of HIV-1 genotypic tropism assays that are highly sensitive and specific for establishing the tropism of HIV-1 subtypes A, B, C, D and circulating recombinant forms of subtypes AE and AG, which together account for 95% of HIV-1 infections worldwide. The PhenoSeq platform will inform the appropriate use of maraviroc and future CCR5 blocking drugs in regions of the world where non-B HIV-1 predominates, which are burdened the most by the HIV-1 pandemic.

AB - Over the past decade antiretroviral drugs have dramatically improved the prognosis for HIV-1 infected individuals, yet achieving better access to vulnerable populations remains a challenge. The principal obstacle to the CCR5-antagonist, maraviroc, from being more widely used in anti-HIV-1 therapy regimens is that the pre-treatment genotypic œ tropism tests to determine virus susceptibility to maraviroc have been developed primarily for HIV-1 subtype B strains, which account for only 10% of infections worldwide. We therefore developed PhenoSeq, a suite of HIV-1 genotypic tropism assays that are highly sensitive and specific for establishing the tropism of HIV-1 subtypes A, B, C, D and circulating recombinant forms of subtypes AE and AG, which together account for 95% of HIV-1 infections worldwide. The PhenoSeq platform will inform the appropriate use of maraviroc and future CCR5 blocking drugs in regions of the world where non-B HIV-1 predominates, which are burdened the most by the HIV-1 pandemic.

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DO - 10.1038/srep08543

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SN - 2045-2322

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Reliable genotypic tropism tests for the major HIV-1 subtypes

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