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HIV Drug Resistance

Patients who are infected with human immunodeficiency virus (HIV) are treated with anti-retroviral therapy (ART), which has significantly reduced HIV-associated morbidity and mortality. The emergence of ART resistance prevents a sustained virologic response to treatment and reduces effective therapeutic options. Approximately 68% of patients have developed resistance to at least 1 ART drug. These patients can benefit from testing for ART drug resistance.

Antiretroviral resistance testing is conducted in 2 ways: (1) genotypic testing sequences HIV RNA and compares it with a database of known drug resistance mutations to determine which medications it is resistant to; and (2) phenotypic testing measures susceptibility of HIV to ART to specific antiretroviral drugs in a controlled environment.

Monogram Biosciences offers both genotype and phenotype assays for HIV antiretroviral drug resistance. Both genotyping and phenotyping technology start out in much the same way. The patient’s viral RNA is isolated, and the section to be tested is excised, converted to DNA by reverse transcription, and then amplified via PCR.

For a genotype, the amplified patient viral DNA is sequenced, compared to a wild-type reference sequence, then a prediction of drug susceptibility is made based on differences noted during the comparison. Thus, genotyping technology provides a prediction of drug susceptibility.

Monogram offers two options for genotypic resistance testing for HIV: GenoSurePRIme® and GenoSure® MG. Both tests provide predictions of resistance for all nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). GenoSurePRIme® provides additional information about integrase inhibitors.

Monogram’s phenotyping test is called PhenoSense. For a phenotype, the amplified viral DNA segments are inserted into vector constructs and pseudovirions are created by transfecting these vectors with HIV virus constructs. The activity of a patient’s HIV in the presence of the antiretroviral drugs is compared to the activity of a control strain of HIV that is known to be susceptible to a specific drug. Thus, phenotyping directly measures the ability of HIV to grow in the presence of drugs. This comparison can determine how likely or unlikely a person is to respond to that drug.

Reference

https://www.monogrambio.com/

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