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Australian Researchers Employ POC RNA Testing to Address Growing Rate of HCV Infections

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NEW YORK (360Dx) – Hepatitis C virus RNA testing at the point of care could provide an advantage over antibody testing by enabling diagnosis of active infection in a single visit, according to a recent study conducted by researchers in Australia.

These point-of-care tests can play a vital role to ensure that people receive proper treatment, said Jason Grebely, an associate professor at the Kirby Institute, University of New South Wales in Sydney, Australia, who conducts point-of-care HCV testing for substance users.

With colleagues, Grebely participated in a study, published recently in Lancet Gastroenterology and Hepatology, in which they evaluated the performance of the Cepheid Xpert HCV Viral Load assay at the point of care at five sites in Australia. The sites included three drug and alcohol clinics, one service for the homeless, and one needle and syringe program.  

The researchers found that the assay detected active infection with levels of specificity and sensitivity comparable to that of a popular laboratory test, the Abbott RealTime HCV Viral Load assay.

"Onsite HCV testing is associated with an increased ability to move people to care," said Grebely, who is also the president of the International Network on Hepatitis in Substance Users.

Providing highly sensitive and specific testing results at the point of care leads to broader treatment because it increases the number of people taking tests for HCV, Grebely said. Further, the ability to take blood using a fingerstick instead of a vein puncture can be an important factor driving uptake, especially for people injecting drugs, among whom HCV prevalence is high, he said.

A key component of the Xpert HCV viral load fingerstick test, he said, is that it can detect active viral infection, which is an advance over antibody tests that only indicate previous exposure. The assay provides for a one-step approach to testing, which enables more people to receiving treatment and show up for testing.

To evaluate the sensitivity and specificity of the Cepheid Xpert HCV Viral Load assay at the point of care, the researchers in Australia collected both plasma and finger-stick capillary whole-blood samples from 210 participants in an observational cohort that enrolled at the five sites.

They found that sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in samples collected by finger-stick was 95.5 percent, and specificity was 98.1 percent, and they verified that "the viral load test can effectively detect active infection from a finger-stick sample."

Antibody tests for HCV include rapid diagnostic tests, chemiluminescence assays, and enzyme immunoassays. HCV antibodies can be detected in the blood, usually within two or three months after exposure to the virus.

Clinical challenges arise when "a lot of people who have taken the antibody test do not return for confirmatory RNA testing," which determines whether they have an active virus, he said.

"You have to get the patient back for a second visit, and in a population that's marginalized – including people who are homeless or injecting drugs – getting them to return can be difficult to achieve," he added.

He said that a major issue among people who inject drugs is that they have very poor venous access, so having a fingerstick test circumvents the potentially challenging task of tapping blood from veins. He said that his team saw an opportunity to be the first in the world to evaluate the use of a fingerstick POC test for HCV, and they were able to incorporate it into an existing study where they were looking at liver health promotion and intervention in drug and alcohol clinics, and needle and syringe programs in homelessness settings.

Driving test adoption is critical for an infection that, according to the World Health Organization, causes more than 700,000 deaths annually, and for which less than 15 percent of people are aware that they are chronically infected, Grebely said.

HCV infection is a major cause of chronic liver disease, including cirrhosis and hepatocellular carcinoma. It accounts for one-third, or 34,500, of all hepatocellular carcinoma deaths, according to WHO. The burden of HCV remains disproportionately high in low- and middle-income countries.

Viral hepatitis, which includes hepatitis B and C, "is a major public health challenge that requires an urgent response," according to the WHO's Global Hepatitis Report, 2017. "The disease caused 1.34 million deaths in 2015, a number comparable to annual deaths caused by tuberculosis and higher than those caused by HIV," the report said.

About 325 million worldwide in 2015 were carriers of hepatitis B or C virus infections, which can remain asymptomatic for decades, WHO said, and added that "access to affordable care is disturbingly low."

Testing access, cost, infrastructure, and patient loss are significant barriers to increasing detection rates, as well as care and treatment in resource-limited settings, according to Unitaid, a global health initiative, administered by WHO, whose aim is to end tuberculosis, HIV/AIDS, and malaria epidemics. "It is generally believed that the introduction of appropriate, robust, POC diagnostics for HCV can improve access to testing in developing countries," it said in a report Hepatitis C: Diagnostics Technology Landscape.

Author Maurine Murtagh wrote that although rapid POC assays for detecting anti-HCV antibodies "perform reasonably well when used correctly and are low cost, many of the available tests … are either too complex, expensive, have cold chain requirements, or are not of high quality." Many lack good manufacturing practice and prequalification by WHO or approval by the US Food and Drug Administration or European Union CE marking or equivalent, she wrote.

Fingerstick testing and availability of high-performance tests at the point of care are encouraging adoption, but experts said the global need to address growing levels of HCV requires a multipronged approach. While using a fingerstick instead of venipuncture to access blood is "a neat tool to increase the number of people RNA-tested for active infection, what we really need is to increase the total number of people diagnosed," Grebely said, adding that achieving that will required a combination of strategies that could include antibody, core antigen, RNA, and dried blood spot testing.

Philippa Easterbrook, a senior scientist in the global hepatitis program, HIV department, at the World Health Organization, wrote on behalf of the WHO's Guidelines Development Group in an article published last year in the Journal of Hepatology that "The use of capillary whole blood dried spot specimen collection for both HCV serological and NAT technologies may be considered to facilitate access to testing in certain settings where there are either no facilities or expertise to take venous blood samples; or in persons with poor venous access; or where quality-assured RDTs are not available or their use is not feasible."

Among the overall testing strategies for HCV, Easterbrook recommends use of "a single, quality assured serological assay that meets minimum performance standards — more specifically an immunoassay or rapid diagnostic test." She recommended use of rapid diagnostic tests when laboratory-based tests are unavailable, or when access to these tests would facilitate care and treatment. Easterbrook also recommended use of nucleic acid testing technologies "as the preferred testing strategy to diagnose active HCV infection." However, a core antigen HCV assay may also be considered to detect active infection, she wrote, when the assay has comparable clinical sensitivity to nucleic acid testing technologies.

Cepheid is not alone in recognizing the need and opportunity in POC HCV testing.

In January, Daktari Diagnostics said that it had reached a milestone in a global collaboration with Merck for the development of its rapid point-of-care HCV core antigen confirmatory test system. Daktari has successfully completed the design of the cartridge prototype suitable for commercial production.

The firm noted that its developmental HCV POC system is designed to provide quantitative determination of HCV viral load to confirm diagnosis of an active HCV infection from samples of whole blood. It is based on a high-sensitivity measurement of the HCV core antigen and allows for a single-test approach. The POC system consists of an automated instrument with an integrated reagent cartridge subsystem.

In February, Epistem Holdings said that its Genedrive diagnostic test was cleared for use in clinical trials for HCV testing by the Institut Pasteur in Paris. The Institut’s approval allows clinical trials of the HCV test to commence in anticipation of regulatory approval and market launch in the EU during this year, Epistem said. Genedrive detects viral RNA, covers all HCV genotypes, and is performed at point-of-need medical centers directly on plasma within 90 minutes, the firm said.

Laboratory-based HCV testing solutions also continue to be recognized by regulatory authorities.

In February, Hologic said that the FDA had given premarket approval for use of its Aptima HCV Quant Dx assay on the automated, sample-to-answer Panther system, to quantify hepatitis C viral load and confirm active HCV infection.

In May, researchers at the University of British Columbia's Center for Excellence said that they have developed a next-generation sequencing-based hepatitis C virus test to identify variants that confer resistance to drugs. The NGS test will also serve to genotype the virus, replacing PCR, hybridization, and Sanger-based tests that were not as broad, or did not have as high resolution as NGS.

The Cepheid Xpert HCV Viral Load test received a CE IVD mark in April 2015 for the quantitative, on-demand confirmation of infection and monitoring of hepatitis C virus.

 

 

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