The evaluation of the co-receptor tropism of HIV - the ability to enter cells
via the CXCR4 or CCR5 co-receptor - may provide highly useful information at
many stages of HIV disease and antiretroviral therapy. In particular, measuring
the tropism of HIV is likely to be important for screening patients for
inclusion into clinical trials of co-receptor antagonists and for monitoring of
tropism changes during the treatment. In treatment-naive patients, tropism
information may prove valuable in deciding when to initiate therapy. Monogram's
co-receptor tropism assay, Trofile, measures the ability of a patient virus'
envelope gene to mediate entry into cells expressing CXCR4 or CCR5. The tropism
technology is a modification of the PhenoSense entry inhibitor assay and is
widely used by pharmaceutical companies in preclinical development and clinical
trials to evaluate the HIV tropism. Specifically, in Pfizer's maraviroc Phase
III trials, the assay has been used to screen over 5100 patients to
characterize baseline tropism, and at subsequent time points to provide an
understanding of why patients may experience treatment failure on the drug.
clonal analyses have
been conducted to provide in-depth information on viral behavior during the
course of the trial.*
Trofile can also be used to characterize early stage compounds by testing them
against a panel of CXCR4, CCR5, Dual and Mixed tropic viruses of multiple
Reference: Westby, M., Lewis, M., Whitcomb, J., Youle, M., Pozniak, A. L.,
James, I. T., Jenkins, T. M., Perros, M., and van der Ryst, E.
Emergence of CXCR4-Using Human Immunodeficiency Virus Type 1 (HIV-1) Variants
in a Minority of HIV-1-Infected Patients following Treatment with the CCR5
Antagonist Maraviroc Is from a Pretreatment CXCR4-Using Virus Reservoir. J
Reference: Whitcomb, J., Huang, W., Fransen, S., Limoli, K., Toma, J., Wrin, T.,
Chappey, C., Kiss, L., Paxinos, E. E., & Petropoulos, C. J.
Development and Characterization of a Novel Single-Cycle Recombinant Virus
Assay to Determine Human Immunodeficiency Virus Type-1 Co-Receptor Tropism. Antimicrob
Agents Chemother 51, in press (2007).
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