Genotype tests

Based on HIV-1 drug resistance genotypic test results at the Screening Visit and prior treatment history, the investigator considers lopinavir/ritonavir plus at least two NRTIs to be an appropriate treatment for the subject. 

Allorge, D., Hamdan, R., Broly, F., Libersa, C., and Colombel, J. F. (2005) ITPA genotyping test does not improve detection of Crohn s disease patients at risk of azathioprine/6-mercap-topuiine induced myelosuppression. Gut. 54, 565-568. 

More prospective studies are needed to test the feasibility and cost effectiveness of using algorithms based on these parameters for adjusting initial warfarin dose to meet individual needs, but the data at present make a strong case for the use of CYP2C9 genotyping testing prior to warfarin treatment, especially in the elderly. 

Why would genotyping tests be ordered and when The intended use of the test is usually to reduce adverse events by more precise dosing in at risk genotypes defined by the tests. Possible scenarios include a priori testing followed by tailored initial dosing in patients at-risk, e.g., patients with heart disease who need a... 

Mutations in HIV accumulate and interact with each other and cause resistance to one drug and then others, one of the pivotal problems in treatment. In the past, the complexity of HIV drug-resistance testing and the limited information on its clinical utility made routine application impractical. Recent advances in automated assay technology have allowed rapid characterization of HIV in blood samples, so an increasing number of commercial laboratories now offer phenotypic and genotypic testing. 

Short-day treatments of 11 hours induced flowering in most genotypes tested. 

CYP3A4 and CYP3A5 genotyping tests could not explain sufficiently the inter-individual variability observed in midazolam pharmacokinetics (Eap 2004). 

Both genotypic and phenotypic drug resistance assays are valuable tools in this respect. Where genotypic tests are fast and relatively cheap to monitor the presence of known resistance-related mutations, they suffer from known and unknown synergistic and antagonizing effects of combinations of mutations. Only phenotypic assays can measure the actual inhibitory effects of the antiviral drugs on the clinical HIV-1 isolate. Specific reverse transcriptase (RT) and... 

In Subheading 5. a few genotypic tests will be described. Using phenotypic assays, clinical isolates that display various levels of resistance to particular drugs have been identified. Often the researcher wants to know what mutations are responsible for this phenotypic resistance, in an attempt to understand and possibly to anticipate the development of the resistance. Because present-day clinical anti-HIV drugs are RT or protease inhibitors, sequencing protocols for clinical HIV-1 RT and protease genes will be described. Once researchers have established a stable relationship between resistance and particular mutations, tests that identify specific mutations may be very valuable and much faster than any other method. In this respect, the protocol for two amplification refractory mutation systems (ARMS) will be described, which use mutation-specific PCRs. Other useful assays are the point mutation assay (10) and LiPA (see also Chapter 10). 

Genotyping tests, however, may not detect TPMT deficiency in all patients, particularly those with a rare unknown but clinically significant variant. Compound 1 erozygotes also present a challenge to PCR-based ge ... 

Coty B, ReedM, Jacobs A, etal. Development and evaluation of an eSensor genotyping test for CYP450 2C9 and VKORCl polymorphisms Available at http //www.osmetech.com/ pdf/PosterAMPll-07.pdf. Accessed July 27, 2008. 

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