Reliable genotypic tropism tests for the major HIV-1 subtypes

Sci Rep. 2015 Feb 25:5:8543. doi: 10.1038/srep08543.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Amino Acid Sequence
  • CCR5 Receptor Antagonists / therapeutic use
  • Computational Biology
  • Cyclohexanes / therapeutic use
  • Genotype
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / drug therapy
  • HIV-1 / physiology*
  • Humans
  • Maraviroc
  • Mutation
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phenotype
  • Receptors, CCR5 / chemistry
  • Receptors, CCR5 / metabolism
  • Triazoles / therapeutic use
  • Viral Tropism / genetics*

Substances

  • CCR5 Receptor Antagonists
  • Cyclohexanes
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • Receptors, CCR5
  • Triazoles
  • Maraviroc