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Researchers develop assay that could identify treatment strategies for HCV

A new capture-fusion assay was accurate in testing sensitivity of different antiviral drugs, suggesting it may be effective for determining treatment strategies for patients with hepatitis C virus infection.

“We have developed a capture-fusion assay that permits replication of patient-derived HCV of all vital genotypes in vitro and enables testing of sensitivity to antiviral drugs. … [It] may help identify the most appropriate treatment strategy for patients with chronic HCV,” the researchers wrote.

To create the phenotyping assay, researchers studied monocytes from patients with HCV and sought to develop a model based on patient-derived HCV observed by the cell line THP-1 and “replication assessed after fusion to hepatoma cells,” according to the research.

In doing so, they found that monocytes from patients with HCV harbor the virus that replicates when cells are fused to hepatocytes.

“THP-1 cells incubated with infected sera capture HCV, which replicates when fused to hepatocytes,” the researchers wrote.

All HCV genotypes were replicated from 52 isolates (n = 42), and then sensitivity of Incivek (telaprevir, Vertex Pharmaceuticals) and alisporivir (Debio 025, Debiopharm Group) in the different genotypes was measured.

Overall, there were differences observed in 50% inhibitory concentration (IC₅₀) which correlated with clinical response (telaprevir IC₅₀ for genotype 1 was 0.042 ± 0.003 and 0.117 ± 0.015 μM for genotype 3 vs. alisporivir IC₅₀ for genotype 1 was 0.139 ± 0.013 and 0.044 ± 0.007 μM for genotype 3).

Changes in IC₅₀ were also observed after the identification of telaprevir-resistant viral isolates. For example, one patient experienced a poor clinical response to telaprevir and wild-type viral sequence showed telaprevir sensitivity decreased using the capture-fusion assay.

In addition, samples from a 2-week telaprevir monotherapy study showed five of eight patients with HCV genotype 3 did not respond compared with three of eight patients who did. The research stated that the “capture-fusion assay correctly identified responders,” according to the researchers.

The researchers concluded: “Genotype-specific responses to novel antiviral drugs and detection of resistant viral strains have been demonstrated. [Interferon]-responsive or poorly responsive viral strains can be distinguished, and the assay can identify the subgroup of patients with [HCV genotype 3] who respond to [telaprevir].”

Disclosure: Cunningham reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.