A genotypic test is just as accurate as a more expensive tropism test in determining which treatment-experienced patients are suitable for treatment with the CCR5 inhibitor maraviroc, researchers from the University of British Columbia reported on Wednesday, July 22 at the Fifth International AIDS Society conference in Cape Town.
The finding opens the prospect for much cheaper testing to determine susceptibility to CCR5 inhibitor treatment, and coincides with a re-analysis of 96-week results from the MERIT study showing that maraviroc is as effective as efavirenz in treatment-naive patients, albeit better tolerated.
Currently, in order to determine whether a person has HIV that is susceptible to a CCR5 inhibitor, the so-called tropism assay (Trofile; Monogram Biosciences) is the only current means of determining which patients will benefit from a CCR5 inhibitor.
The drawbacks of the Trofile assay are its cost (launched in 2007 at around US $1950 per test), the turnaround time for results – up to three weeks, and the fact that it can only be used when viral load is >1000 copies/ml.
The alternative is to look at a region of HIV’s envelope protein, the V3 loop, to determine tropism. This can be done during a standard genotyping test for drug resistance, at no extra cost. The genotype is then used to predict the phenotype, or tropism, an approach called “geno2pheno.”
The study by Harrigan et al from the University of British Columbia Centre for Excellence in HIV/AIDS, Vancouver, analyzed the performance of the two tests in predicting virological response to maraviroc in treatment-experienced patients who participated in MOTIVATE 1 (N=1216) and 2 (N=999) and in the A4001029 study (N=165).
Using stored blood samples, the researchers compared the ability of the baseline testing methods to predict virologic response to treatment at weeks 8 and 24. They found that the Trofile assay and genotyping produced comparable results in terms of detecting viral phenotype and in predicting virologic response, regardless of patient characteristics.
Based on viral tropism and the degree of genotypic sensitivity to drugs in the background regimen, the researchers were also able to predict the degree of virologic suppression and the proportion of patients with viral load <50 copies/mL, and found very high levels of agreement between the two assays. Patients identified as CCR5-tropic had almost identical degrees of viral load reduction (-2.5 log10 at week 8).
The investigators concluded that “HIV V3 genotyping shows promise as a significantly faster and more cost-effective way to correctly identify patients who would benefit from CCR5 antagonists like maraviroc.”
The study was supported by maraviroc’s manufacturer, Pfizer, as it attempts to breathe new life into maraviroc sales. According to Pharmacogenomics Reporter (www.genomeweb.com), Monogram Biosciences is currently testing fewer than 2500 samples per quarter for CCR5 tropism, indicating the small size of the market for a drug that the manufacturer had hoped would be a blockbuster HIV product.
Reference
Harrigan PR et al. Screening for HIV tropism using population-based V3 genotypic analysis: a retrospective virologic outcome analysis using stored plasma screening samples from the MOTIVATE studies of maraviroc in treatment-experienced patients. Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Cape Town, abstract WeLBA101, 2009.
08/03/09
PRN REPORT FROM IAS 2009 CAPE TOWN: New Method to Determine Tropism
Source: Reported from Cape Town for PRN News: Bill Valenti, MD