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Trofile™ Overview

Validation experiments demonstrate that Trofile is 100% sensitive at detecting 0.3% minority X4 variants1

  • Trofile enhancements significantly increase detection sensitivity for X4 envs

Accurate detection of minority CXCR4-using variants is essential for preventing treatment failure with CCR5 antagonists2,3

  • Undetected minority CXCR4-using variants may emerge under CCR5 antagonist drug pressure contributing to virologic failure
  • Sequence-based methods may define patients as having CCR5-tropic (R5) virus when in fact they have dual/mixed (D/M)

Monogram enhances the sensitivity of Trofile™ for even better patient selection

Trofile™ enhanced sensitivity assay predicted early emergence of CXCR4-using virus in a reanalysis of the ACTG-5211 study3

  • Of the vicriviroc recipients reclassified with D/M virus at screen (n=15), 80% had D/M virus by week 8 of the study

Patients defined as R5 by the enhanced Trofile assay had improved response to vicriviroc at 2 and 24 weeks2,3

  • Patients with R5 virus at screen and study entry had significantly greater viral load reductions at 2 and 24 weeks that patients reclassified with D/M virus at screen (P≤0.0003)
  • 55% of patients who were screened as R5 with enhanced Trofile had HIV RNA < 400 copies/mL after 24 weeks vs 48% with standard Trofile

Answers to your questions about Trofile and tropism testing

How is Trofile different from other test methods?
  • Unlike other test methods, Trofile is a direct measure of tropism
  • Trofile uses the complete gp160 coding region of the HIV-1 envelope protein to ensure that all the determinants of tropism are testing 5,6
Why does Trofile use the complete HIV-1 envelope?
  • Both the gp120 (includes the V3 loop) and gp41 viral proteins are necessary for HIV-1 entry5,6
  • pg41 and regions of gp120 outside of V3 can contain determinants of tropism6
Is a V3 loop genotypic assay accurate?
  • Current V3 genotyping algorithms are inadequate for predicting CXCR4 co-receptor use in the clinical setting7
  • There is no commercially available V3 genotypic assay
  • None of the clinical trials with CCR5 antagonists were conducted using genotypic algorithms or sequence-based approaches
Can I use patient's CD4 count to predict tropism?
  • CD4 count alone is considered an unreliable surrogate marker of tropism
  • Although D/M or X4 tropism is more common in patients with lower CD4 counts, R5 tropism is frequently observed in patients with advanced disease8

For more Trofile information, go to www.trofileassay.com.

References: 1. Trinh L, Han D, Huang W, et al. Technical validation of an enhanced Trofile assay for selecting patients for therapy with entry inhibitors targeting CCR5. Presented at: 17th International HIV Drug Resistance Workshop; June 10-14, 2008; Sitges, Spain. 2. Reeves J, Han D, Hunt P, et al. Enhancements to the Trofile™ HIV co-receptor tropism assay enable improved detection of CXCR4-using subpopulations and earlier detection of CXCR4-using viruses in sequential patient samples. Presented at: 3rd International Workshop Targeting HIV Entry; December 7-9, 2007; Washington, DC. 3. Su Z, Reeves J, Krambrink A, et al. Response to vicriviroc in HIV-infected treatment-experienced subjects using an enhanced version of the Trofile HIV co-receptor tropism assay: reanalysis of ACTG5211 results. Presented at: 17th International HIV Drug Resistance Workshop; June 10-14, 2008; Sitges, Spain. 4. Data on file, Monogram Biosciences, Inc. 5. Whitcomb JM, Huang W, Fransen S, et al. Development and characterization of a novel single-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism. Antimicrob Agents Chemother. 2007;51:566-575. 6. Huang W, Toma J, Fransen S, et al. Coreceptor tropism can be influenced by amino acid substitutions in the gp41 transmembrane subunit of human immunodeficiency virus type 1 envelope protein. J Virol. 2008;82:5584-5593. 7. Low AJ, Dong W, Chan D, et al. Current V3 genotyping algorithms are inadequate for predicting X4 co-receptor usage in clinical isolates. AIDS. 2007;21:F17-F24. 8. Wilkin TJ, Su Z, Kuritzkes DR, et al. HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211. Clin Infect Dis. 2007;44:591-595.