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 "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.
authors.affiliation: 1] Center for Biomedical Research, Burnet Institute, Melbourne, Australia 3004 [2] Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia 3010.
authors.forename: Kieran
authors.initials: K
authors.lastname: Cashin
authors.affiliation: 1] Center for Biomedical Research, Burnet Institute, Melbourne, Australia 3004 [2] Department of Infectious Diseases, Monash University, Melbourne, Australia 3800.
authors.forename: Lachlan R
authors.initials: LR
authors.lastname: Gray
authors.affiliation: 1] Center for Biomedical Research, Burnet Institute, Melbourne, Australia 3004 [2] Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia 3010.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Harvey
authors.affiliation: Laboratory of Retrovirology, Centre Recherche Public de la Santé, Luxembourg 1526.
authors.forename: Danielle
authors.initials: D
authors.lastname: Perez-Bercoff
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, Canada Y6Z 1Y6.
authors.forename: Guinevere Q
authors.initials: GQ
authors.lastname: Lee
authors.affiliation: 1] Center for Biomedical Research, Burnet Institute, Melbourne, Australia 3004 [2] Department of Infectious Diseases, Monash University, Melbourne, Australia 3800.
authors.forename: Jasminka
authors.initials: J
authors.lastname: Sterjovski
authors.affiliation: 1] Center for Biomedical Research, Burnet Institute, Melbourne, Australia 3004 [2] Department of Infectious Diseases, Monash University, Melbourne, Australia 3800.
authors.forename: Michael
authors.initials: M
authors.lastname: Roche
authors.affiliation: ViiV Healthcare, Research Triangle Park, North Carolina, USA 27709-3398.
authors.forename: James F
authors.initials: JF
authors.lastname: Demarest
authors.affiliation: ViiV Healthcare Australia, Abbotsford, Australia 3067.
authors.forename: Fraser
authors.initials: F
authors.lastname: Drummond
authors.affiliation: BC Centre for Excellence in HIV/AIDS, Vancouver, Canada Y6Z 1Y6.
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.affiliation: 1] Center for Biomedical Research, Burnet Institute, Melbourne, Australia 3004 [2] Department of Medicine, Monash University, Melbourne, Australia 3800 [3] Department of Microbiology, Monash University, Melbourne, Australia 3800.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Churchill
authors.affiliation: 1] Center for Biomedical Research, Burnet Institute, Melbourne, Australia 3004 [2] Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia 3010 [3] Department of Infectious Diseases, Monash University, Melbourne, Australia 3800 [4] School of Applied Sciences, College of Science, Engineering and Health, RMIT University, Melbourne, Australia 3001.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Gorry
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D065100:CCR5 Receptor Antagonists / Q000627:therapeutic use; D019295:Computational Biology; D003510:Cyclohexanes / Q000627:therapeutic use; D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D000077592:Maraviroc; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism; D014230:Triazoles / Q000627:therapeutic use; D056189:Viral Tropism / Q000235:genetics*
chemical_list: D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019713:Receptors, CCR5; D014230:Triazoles; D000077592:Maraviroc