Assay Measures Susceptibility of HIV to Integrase Inhibitors

A resistance assay directly measures the susceptibility of the human immunodeficiency virus (HIV) to a new and potent class of integrase inhibitor drugs that blocks viral replication by preventing viral genes from integrating into the DNA of newly infected cells.

The new assay is called PhenoSense Integrase. The region of the HIV genome that encodes integrase is amplified from a patient blood sample and inserted into a proprietary test vector that is used to generate virus particles that replicate using the patient virus integrase protein. Completion of a single replication cycle results in the production of luciferase activity in infected cells. Infection in the presence of drug is performed to determine whether a patient virus is sensitive or resistant to integrase inhibitors. Based on the amount of luciferase activity produced in the absence of drug, PhenoSense Integrase also provides a measure of replication capacity (RC) of integrase inhibitor sensitive and resistant viruses.

Monogram Biosciences, Inc. (San Francisco, CA, USA) has announced the launch of the PhenoSense Integrase assay, which was built on Monogram's technology platform, PhenoSense. The performance of the PhenoSense Integrase assay is validated in compliance with regulations specified by the Clinical Laboratories Improvement Amendments (CLIA). It is performed in Monogram's Clinical Reference Laboratory, which is accredited by the College of American Pathologists (CAP; Northfield, IL, USA).

PhenoSense Integrase and other Monogram assays were used to support the clinical trials of the integrase inhibitor, Merck's (Whitehouse Station, NJ, USA) Isentress (raltegravir), which received U.S. Food and Drug Administration (FDA) approval in October 2007. In Merck's phase III Benchmark trials, Monogram's PhenoSenseGT was used to select optimized drug regimens in the placebo and Isentress-containing treatment arms while PhenoSense Integrase was used to identify and characterize Isentress resistant viruses in treatment failures.

"Using new antiretroviral drugs correctly today, including HIV integrase inhibitors, is critically important since the pipeline for additional new agents is not likely to provide treatment options beyond our current choices for a number of years," said Dr. Charles Hicks, associate professor of medicine at Duke University Medical Center (Durham, NC, USA). "Tools like HIV resistance phenotype tests (including Monogram's PhenoSense Integrase and PhenoSense GT assays) and the HIV tropism assay (Trofile) are important tools to help clinicians make good choices. They can also help with modifying regimens that are not suppressive by determining whether additional resistance has emerged and which drugs are no longer active."

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Monogram Biosciences, Inc.
Merck
College of American Pathologists
Duke University Medical Center