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LabCorp Presents New Findings on HIV-1 and HCV Antiviral Drug Resistance at the 2015 Conference on Retroviruses and Opportunistic Infections

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Laboratory Corporation of America® Holdings (LabCorp®) (NYSE: LH) announced today that Monogram Biosciences, Inc., a member of the LabCorp Specialty Testing Group, presented two new studies characterizing HIV-1 and HCV antiviral drug resistance at the 2015 Conference on Retroviruses and Opportunistic Infections (CROI 2015). The conference was held at the Washington State Convention Center, in Seattle, Washington. Monogram’s studies were presented on February 25th and 26th, 2015.

Chronic Human Immunodeficiency Virus Type 1 (HIV-1) infection afflicts approximately 1.2 million individuals in the U.S. Today, HIV-1 infections are effectively treated with potent combinations of antiretroviral (ARV) drugs. However, current treatment protocols must be maintained over the life of the individual, and the emergence of drug resistant virus variants is a persistent threat to durable viral suppression.

In a study entitled “Dolutegravir Resistance Requires Multiple Primary Mutations in HIV-1 Integrase,” Monogram investigators demonstrate that resistance to dolutegravir, the newest member of the HIV-1 integrase inhibitor drug class, requires combinations of mutations known to confer resistance to this drug class. Using Monogram’s proprietary PhenoSense® HIV drug resistance platform, the investigators associate quantitative reductions in dolutegravir sensitivity with specific combinations of mutations that confer integrase inhibitor resistance. This finding supports the favorable response rates observed in patient populations treated with regimens that incorporate dolutegravir following prior treatment failure with an integrase inhibitor–containing regimen.

Approximately 3.2 million individuals in the U.S. are chronically infected with Hepatitis C Virus (HCV). While recent advances in treatment with new, potent antiviral drugs have dramatically improved cure rates for a significant subset of HCV strains, the vast genetic diversity of HCV remains a formidable challenge for the universal treatment of HCV infection. Inhibitors of the non-structural protein 5A (NS5A) are potent antagonists of HCV replication; however, the mutation barrier to acquired resistance is low, and in some cases, resistance may exist naturally.

In a study entitled “Characterization of Naturally Occurring Resistance to HCV NS5A Inhibitors,” Monogram investigators study the viruses of treatment naïve individuals infected with HCV genotype 1 (GT1) for the presence of mutations that are associated with NS5A inhibitor resistance. Using Monogram’s proprietary HCV GenoSure® NS5A Assay and a sensitive next generation sequencing approach, the investigators are able to detect pre-existing resistant variants within patient virus populations belonging to the two major HCV subtypes (GT1a and GT1b) that circulate in the U.S. Naturally occurring NS5A resistance mutations are more varied among GT1a viruses compared to GT1b viruses. GT1a viruses are also more likely to contain more than one NS5A inhibitor resistance mutation. In addition, the investigators demonstrate that the size of the subpopulations of resistant variants within GT1a viruses is larger compared to GT1b viruses. Finally, using Monogram’s proprietary PhenoSense® HCV drug resistance assay, the investigators demonstrate that NS5A mutations confer larger reductions in NS5A inhibitor susceptibility in the context of GT1a sequences compared to GT1b sequences. Overall, these observations suggest that GT1a viruses may be more prone to naturally-occurring and acquired NS5A inhibitor resistance than GT1b viruses.

“These two studies demonstrate the advantages of using state of the art DNA sequencing and cell-based infectivity assays to investigate antiviral drug resistance,” stated Dr. Marcia Eisenberg, LabCorp Diagnostics’ Chief Scientific Officer. “This comprehensive approach improves our ability to accurately decipher the genetic determinants of drug resistance, which can be valuable to the introduction of new drugs and new drug classes into routine clinical practice.”

In these studies, Monogram investigators utilized the Company’s proprietary GenoSure platform for nucleic acid sequencing, and its proprietary PhenoSense platform for cell-based infectivity, to detect and quantify alterations in antiviral drug susceptibility conferred by specific mutation profiles. PhenoSense and GenoSure are offered exclusively through LabCorp and Monogram. GenoSure assays are used clinically to personalize antiviral drug treatments for HIV and HCV patients and in drug development to characterize mutation profiles associated with resistance to new anti-HIV and anti-HCV drug candidates. PhenoSense assays are used in drug development to directly measure resistance to new anti-HIV and anti-HCV drug candidates, and in the clinic to personalize antiviral drug treatments for HIV patients. Monogram is an established innovator and industry leader in antiviral drug resistance testing. LabCorp has long been committed to serving patients afflicted with serious viral infections and is an industry leader in developing and providing assays to support diagnosis, prognosis and treatment of viral diseases.

Source: MarketWatch