Blood tests lead the way to better diagnoses at AACC: high-tech next-generation sequencing and faster-than-ever blood tests are just two advances the clinical chemistry industry is looking toward to enable more effective treatment.
Currently, the gold standard for treating HIV is a combination of antiretroviral medicines--usually three or more--called antiretroviral therapy, or ART. The medicine combo slows the rate at which HIV makes copies of itself in the body. This has proven effective, with more and more HIV-positive people living long lives. The flipside is that this means an HIV-positive person is reliant upon pills for the majority of his/her life. Combine that situation with worldwide HIV/AIDS eradication efforts and, naturally, the use of antiretroviral therapy has increased dramatically in the last 15 years. So too, then, has the occurrence of HIV drug resistance.
There are no clear statistics on how many people with HIV are partially or fully drug resistant. The World Health Organization (WHO) estimates that in the U.S., Japan, Europe and Australia, the rate of transmitted drug resistance hovers between 10 and 17 percent. But that's only newly infected individuals--not those who are treatment-experienced.
At AACC, Singaporean researchers debuted a first-of-its-kind next-generation sequencing test that can detect HIV drug resistance mutations that conventional tests fail to identify. Currently, the only test on the market dates to the early 2000s, and is based on Sanger sequencing, an older technology that is expensive, can take one to two weeks to produce results and has low sensitivity for drug resistance mutations that occur at a frequency below 15 to 20 percent.
Known as the Sentosa SQ HIV-1 genotyping assay, the new test, developed by Gerd Michel, Charlie Lee and Elian Rakhmanaliev from Vela Diagnostics, relies on automated sample processing and analysis with integrated software. To evaluate the efficacy of the Sentosa, the researchers compared its performance with that of a Sanger sequencing-based test, the TruGene HIV-1 genotyping kit.
The researchers tested 111 blood samples from HIV-1 patients for mutations in the virus's protease and reverse transcriptase genes, which are the two main genes that are typically analyzed in drug resistance testing. The Sentosa demonstrated unprecedented sensitivity, detecting 100 percent of all drug resistance mutations in the protease gene compared to 90.45 percent detected by the TruGene. The Sentosa also identified 98.16 percent of all drug resistance mutations in the reverse transcriptase gene compared to 74.48 percent identified by the TruGene.
In total, the Sentosa--which produces results in 2.5 days--detected 130 drug resistance mutations not found by the TruGene, while the TruGene only found eight drug resistance mutations that the Sentosa missed.
"To our knowledge, nobody else has developed an assay like this," Michel said in a press release. "Now we have the opportunity to do HIV drug resistance testing much faster, at a lower cost and also to test for mutations that are not visible with Sanger sequencing. The impact of these mutations that have not been seen by Sanger is not known yet. But now we have the tools to detect them so that researchers can determine how relevant they are clinically and physicians can determine if there should be a change in treatment."
All about blood
Given their importance to clinical applications, new blood tests are always well represented at AACC. Last year, blood tests debuted for prenatal checks, diabetes and Ebola, among other diseases. This year, scientists from Randox Laboratories unveiled a biochip-based blood test that helps identify who is at an elevated risk of Alzheimer's disease.
According to the scientists, the test detects the presence of a protein in the blood produced by a specific variation of the apolipoprotein gene (ApoE4), which is associated with an increased risk of developing Alzheimer's disease. Researchers verified the accuracy of the biochip test by comparing the results of 384 samples to those from a standard molecular diagnostic test. The two tests were in 100 percent agreement.
Keeping with the goal of providing better, faster and more accurate diagnosis, the biochip test can run multiple tests on just one sample of blood, producing results in only three hours--quicker and more affordable than the standard DNA test.
Another blood test was revealed during a special session given by Elizabeth Holmes, embattled CEO of Theranos. During "The Miniaturization of Laboratory Testing," Holmes introduced the miniLab--a desktop automated device used as a single platform that can carry out a variety of diagnostic tests, some using as little as 160 microliters of blood (which is equivalent to a few drops via finger-prick).
According to Theranos, the miniLab comprises a multi-channel material-handling robot that can perform tasks on samples that may traditionally require manual processing. A disposable cartridge that houses reagents, liquid handling tips, reaction cuvettes and other consumables was designed to work with the robot to facilitate a range of tests using different methodologies inside the miniLab. The Theranos Virtual Analyzer (TVA) is designed to facilitate two-way communication with the miniLab, allowing for control of processes and interpretation of results, all remotely. These results could then be interpreted in a central laboratory.
During the session, Holmes presented 16 studies on miniLab performance data across a sampling of testing categories and methods. For example, she presented data showing the miniLab churning out reproducible results when testing for lymphocytes and lipid levels. Holmes also showed data that compared its lipid test to a comparator test; Theranos was able to confirm the accuracy of its tests against a reference standard from NIST.
Additionally, Holmes released results on the nucleic acid detection capabilities of the miniLab, and discussed the company's Zika nucleic acid-amplification-based assay. The company collected finger-prink blood samples from subjects, including in the Dominican Republic, and shipped them to Palo Alto to run on the miniLab. An analysis of 180 samples showed that the miniLab test had 95.6 percent negative agreement and 100 percent positive agreement with a comparator test, yielding 96 percent sensitivity at a limit of detection of 480 copies/mL for the virus. Theranos has already submitted validation data for its Zika assay to the FDA for an Emergency Use Authorization.
While Holmes presented clinical data said to demonstrate how the miniLab effectively runs diagnostic tests on a few drops of blood, she did not provide data verified by independent or peer-review sources--which is what got Theranos in troube in the first place.
Theranos' data secrecy and refusal to submit to peer review has long been a problem in the scientific community--something that was brought into the spotlight when Theranos voided all results from its Edison device for 2014 and 2015. The FDA also deemed the Edison's propriety Nanotainers--used to collect finger-prick blood--as an "uncleared medical device." The agency revoked the operating license of one of Theranos' labs, and banned Holmes from owning or operating a laboratory for two years--a sanction she can appeal.
However, Holmes did say Theranos will be working with academic institutions and other independent parties to both validate and publish future results. She also said Theranos hopes to achieve FDA market authorizations of the miniLab and other technologies in the coming years.
According to the AACC, a total of 20,000 laboratory medicine professionals registered for the meeting--a 14 percent increase over meeting attendance in 2015, and the highest number of attendees that have come to the meeting in the last four years.
By Michelle Taylor, Editor-in-Chief
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|Title Annotation:||INSTRUMENTATION & EQUIPMENT|
|Date:||Sep 1, 2016|
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