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Available Assays: There are two high-throughput phenotypic assays: Phenoscript (VIRalliance, Paris, France) and Trofile (Monogram Biosciences, Inc., San Francisco CA). Only the Trofile is currently available, a viral load of ≥1000 c/mL is required, the cost $1,960/test and the turnaround time is about 2 weeks (see www.trofileassay.com or call 1-800- 777-0177). The indication for the test is consideration of use of a CCR5 antagonist, since the drug should be used only in patients with pure R5 tropism. In MOTIVATE 1 and 2 the number of treatment experienced patients with exclusive R5 virus was 56% of 2560 screened participants. The infrequency of R5 virus exclusively correlated with CD4 count: It was 76% in 129 patients with CD4 counts >400/mm3 and 40% for patients with <50/mm3. Treatment with maraviroc (MVC) in this subset showed a mean 1.96 log10 c/mL reduction in VL at 24 weeks compared to < 1.0 log10 c/mL reduction in those who received only the optimized background regimen (Nelson M and Lalezari J, et al. 14th CROI 2007, Los Angeles, CA, Abst. 104 A and B). Although all participants had to have R5 tropism at screening to enter the trial, 8% were found to have D/M virus on a second tropism assay at baseline (start of therapy). The virologic response to MVC therapy was poor in those patients. Retrospective analysis using the enhanced Tophile assay (see pg 46) fould an additional. Attempts to measure tropism using cheaper genotype methods have so far been unsuccessful because of limited sensitivity (15th CROI 2008, Boston, MA, Abstr. 920A).
Accuracy of the assay is limited by detection of minority variants. The initial Trofile assay showed 100% specificity for variants present at 10% of the population, but the initial sensitivity of this test fell to 85% for variants making up 5% of the population. (Antimicrob Ag Chemother 2007; 51:566; J Clin Micro 2007;45:279). An "enhanced tropism assay"from Trophile was
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TABLE 2-15: