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VIRTUAL PHENOTYPE: The VircoTYPE assay (Virco) uses the Virtual Phenotype approach to predict the phenotype based on genotypic analysis. The prediction is based on algorithms derived from a large database of samples with paired genotype and phenotype assays.
RELATIVE MERITS: Genotypic resistance tests are generally preferred for baseline (pretreatment) testing, with early failures in which multiple mutations are not expected, and in patients who have discontinued therapy. Arguments for this approach are that genotypes are easy to interpret at early stages of failure and are more sensitive for detecting wild-type/mutant mixtures which may be present in treatment-naïve patients or in patients who have discontinued therapy. In addition, clinical trials demonstrated better outcomes in this setting when compared to the standard of care (GART [AIDS 2000;14:F83], VIRADAPT [Lancet 1999;353:2195]; HAVANA [AIDS 2002;16:209]) or when compared to phenotypic testing (REALVIRFEN [Antivir Ther 2003;8:577]; NARVAL [Antivir Ther 2003;8: 427]). Genotypic testing is less expensive and appears cost-effective when used for first or second regimen failures (Ann Intern Med 2001;134:440; JAIDS 2000; 24:227). Phenotype resistance may be preferred or may supplement genotypic test results in patients with more extensive resistance after multiple regimen failures (CID 2004;38:723) and TORO (NEJM 2003; 348:2175). Phenotypes provide quantitative results, allowing comparison of relative susceptibility and resistance. They assess interactions among mutations, and may be preferable for the assessment of susceptibility to new drugs for which genotype correlates of resistance have not been completely determined. In the POWER studies, phenotypic susceptibility to darunavir was the best predictor of response to therapy (Antiviral Ther 2006;11:S83.)
CCR5 Tropism assay: Tropism assays are used to determine whether patients are candidates for therapy with CCR5 antagonists, which are indicated only in patients with exclusively R5-tropic virus.
Background : HIV binds to the host CD4 cell by attachment of gp120 to a CD4 receptor. This results in a conformational change in gp120 that allows binding to one of two chemokine co-receptors on the CD4 cell surface: CCR5 or CXCR4. There are four categories of tropism:
- R5-tropism: Viruses that bind only to the CCR5 co-receptor
- X4-tropism: Viruses that bind only to the CXCR4 co-receptor
- Dual-tropism: Viruses that can bind to either co-receptor
- Mixed-tropism: Mixed populations that include both R5-tropic and X4-tropic viruses.
Tropism assays cannot distinguish between dual- and mixed-tropic virus; therefore, these viruses are collectively referred to as dual/mixed (D/M)-tropic virus.
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