Singapore-based Vela Diagnostics Holding Pte. Ltd. has received U.S. FDA authorization via the de novo approval pathway for an in vitro diagnostic test to detect HIV-1 genomic drug resistance mutations (DRMs). The Sentosa SQ HIV-1 Genotyping Assay – the first HIV-1 genotyping next-generation sequencing (NGS) assay to win an FDA nod – uses plasma of patients infected with HIV-1 to detect HIV-1 Group M DRMs in the protease, reverse transcriptase and integrase regions of the pol gene in a single test.
Pol gene refers to DNA polymerase and is a gene found in retroviruses. Antiviral therapy (ART) is the current standard of care for patients with HIV-1, and patients' viral loads are monitored to determine how effectively the therapy is working. An uptick in viral load is a sign that the virus may have mutated, meaning a patient's regimen of ART drugs is no longer suppressing the virus and new drugs are needed. The Sentosa SQ HIV-1 test is specifically designed to detect resistance to HIV-1 drugs in patients who are on or about to begin antiviral therapy. It is not intended for diagnosing HIV infection.
"According to a recent report from the Centers for Disease Control and Prevention and the World Health Organization, the percentage of people living with HIV around the world that have resistance to some HIV drugs has increased from 11% to 29% since 2001," said Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, in announcing the novel assay. "Today's authorization can help health care providers better tailor drug treatment for patients who are beginning antiviral therapy and also for those who have developed resistance to HIV drugs by helping to identify mutations in the HIV-1 virus that can impact the effectiveness of certain drugs."
High sensitivity and specificity
The agency approved the Sentosa SQ assay based on studies that demonstrated 95% sensitivity and specificity in detecting 342 HIV drug-resistant mutations. It is meant to be part of a larger toolset in managing patients with HIV-1, along with clinical observations, patient history and other laboratory results.
FDA created the de novo pathway to classify novel medical devices for which general or special controls are deemed sufficient to ensure safety and effectiveness for the intended use, but for which no predicate exists on the market. Devices that are classified as class I or II via a de novo request may serve as predicates for future 510(k) submissions. In granting de novo authorization to the Sentosa SQ HIV-1 test, the FDA said it will establish requirements for accuracy, reliability and effectiveness of future tests to identify viral mutations.
"The granting of the de novo designation of our NGS assay by the U.S. FDA is a major milestone in HIV diagnostics," said Sam Dajani, acting CEO and board chairman of Vela Diagnostics USA Inc., which submitted the de novo request. "With the Sentosa SQ HIV-1 Genotyping Assay, laboratories will now have a sample-to-report solution to aid in monitoring and treating HIV-1 infection."
The HIV genotyping and DRM assay is validated on the Sentosa NGS workflow, which facilitates automated RNA extraction, cataloging, template preparation, sequencing, data analysis, reporting and traceability.
An earlier version of the Sentosa SQ HIV-1 assay was CE-marked in 2017 and subsequently approved for use in Australia and Singapore. The Thai FDA approved the assay in August of this year. The latest configuration, which received the FDA de novo designation, was developed and validated in collaboration with the Mayo Clinic. It is currently undergoing review for the CE mark and by Singapore's Health Sciences Agency.
New HIV strain identified
In related news, Abbott Laboratories reported that a team of company scientists had identified a new subtype of the virus called HIV-1 Group M, subtype L. The research represents the first time that a new subtype of Group M HIV – the cause of the global pandemic - has been verified since 2000 when guidelines were established for classifying new HIV strains, the Abbott Park, Ill., company said.
To ensure that a strain of the virus is indeed a new HIV subtype, researchers must produce three independent cases. Abbott said that the first two samples of subtype L were discovered in the Democratic Republic of Congo, the earliest known site of HIV, in the 1980s and 1990s. A third specimen was collected in 2001, but was hard to sequence due to the amount of virus in the sample and state of sequencing technology at the time. Using current NGS technology, Abbott scientists developed and deployed new approaches to home in on the virus contained in the sample to create a unique genomic fingerprint.
"Identifying new viruses such as this one is like searching for a needle in a haystack," said Mary Rodgers, a principal scientists and head of Abbott's Global Viral Surveillance Program, Diagnostics, and one of the study authors. "By advancing our techniques and using next-generation sequencing technology, we are pulling the needle out with a magnet. This scientific discovery can help us ensure we are stopping new pandemics in their tracks."