Corporate Banner
Satellite Banner
Molecular & Clinical Diagnostics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

HIV Genotypic Sequencing Test Comparable to Standard Phenotypic Test in Predicting Antiretroviral Response

Published: Wednesday, October 03, 2012
Last Updated: Wednesday, October 03, 2012
Bookmark and Share
Genotypic HIV tropism laboratory-developed testing service now available nationally for HIV-infected patients.

A laboratory-developed blood test that uses deep-sequencing technology performed comparably to the industry's standard phenotypic test in helping to predict potential clinical response to HIV-1 antiretroviral CCR5-antagonist therapy, according to a new study from researchers at Quest Diagnostics and Pfizer. The findings underscore the potential of advanced sequencing technologies to aid in the cost-effective management of patients infected with HIV using CCR5 antagonists.

The study, "A Genotypic Test for HIV-1 Tropism Combining Sanger Sequencing with Ultradeep Sequencing Predicts Virologic Response in Treatment-Experienced Patients," was published online September 27 in the peer-reviewed, open-access journal PLOS ONE: http://dx.plos.org/10.1371/journal.pone.0046334.

"Phenotyping to identify HIV tropism has played a critical role for the past five years in disease management for thousands of HIV-infected patients in the United States," said study investigator Rick L. Pesano, M.D., Ph.D., medical director, infectious diseases, Quest Diagnostics. "By demonstrating that faster, more cost-effective viral-genomic sequencing performs comparably to phenotypic testing, our study suggests another option for determining HIV tropism, an essential step in determining if a CCR5 antagonist therapy is a potential treatment option."

The study compared the performance of a genotypic laboratory-developed test from Quest Diagnostics to a widely offered phenotypic laboratory test in the United States to determine HIV-1 tropism on patient samples. Tropism refers to the type of cellular co-receptor, CCR5 or CXCR4, through which HIV-1 infects human cells. Viruses that use CCR5 are called R5-tropic ("R5") and those that use CXCR4 are called X4-tropic ("X4").  CCR5 antagonists can reduce HIV-1 viral loads in patients with only R5 virus, but are not recommended in patients with X4 virus or a dual-mixed combination of R5/X4.

Tropism varies by patient, and X4 virus may emerge over time in patients initially infected with R5 virus. Phenotyping examines the ability of the patient's cloned virus to infect cells, while genotypic tests examine the genetic sequence of the patient's virus. Although phenotyping has been the standard tropism detection method in the United States, genotypic tropism tests are widely used and supported by medical guidelines in Europe.

The Quest Diagnostics laboratory-developed test used in the study employed triplicate population sequencing (TPS), which involves genotyping the third variable (V3) loop, a region of the virus that binds to the CCR5 or CXCR4 co-receptor, and bioinformatics, to infer tropism in patients harboring R5, X4 or dual-mixed virus. A highly sensitive test is required to ensure the detection of X4 virus and exclude patients with low levels of X4 virus from receiving CCR5 antagonist therapy. For this reason, if TPS only detected R5 virus, highly sensitive ultradeep sequencing (UDS), which is able to detect minority X4 HIV-1 variants, was performed as a "reflex" test.

Researchers found that the genotypic and phenotypic tests performed comparably at predicting response in patients undergoing therapy with maraviroc. At week eight, the positive predictive value was 66% for the phenotypic test and 65% for the genotypic test, and negative predictive values were 59% for phenotyping and 58% for genotyping.

Quest Diagnostics launched the Quest Diagnostics HIV-1 Tropism with Reflex to Ultradeep sequencing (UDS) laboratory-developed testing service, based on the genotypic-tropism testing technique used in the study, in June 2012. It is the first genotypic-tropism testing service available to physicians in the United States to demonstrate comparable performance to phenotyping in aiding the selection of patients for potential treatment with CCR5 antagonists. The company's laboratory in San Juan Capistrano, California, developed, validated and performs the testing service for clinicians nationally.

Quest Diagnostics can provide results from the testing service in approximately a week for samples with a TPS result of X4 and in as little as 10 days for samples reflexed to UDS, compared to reported turnaround times of approximately 14 days for the phenotyping test used in the study.

"It is gratifying that sequencing has advanced to a level of sophistication that now enables it to perform comparably to phenotyping," said study investigator Ron M. Kagan Ph.D., director of Bioinformatics, Infectious Diseases, for the Quest Diagnostics Nichols Institute, an advanced test research and development center. "Quest Diagnostics has a strong record of innovation in HIV testing, and we look forward to exploring further the potential of genetic sequencing, and UDS in particular, as tools for helping to manage HIV disease in other applications."

Study Strengths and Limitations

The study's strengths include its use of 327 de-identified samples from the MOTIVATE and A4001029 clinical trials, including clinical outcome data, that were part of the data submitted to the FDA for market approval of maraviroc. Although the study was retrospective, its inclusion of de-identified samples from patients from both studies helped to ensure that patients were included in the study who received maraviroc regardless of their viral tropism status, reducing the bias from using samples previously screened with the first commercial phenotyping laboratory test in the U.S.  Limitations include the use of specimens from only treatment-experienced patients, although prior studies demonstrate that UDS effectively detects tropism in treatment-naive patients, and the use of algorithms focused on HIV-1 subtype B, which, while found in the vast majority of U.S. HIV-1 infected patients, is less common outside the U.S.

The MOTIVATE and A4001029 protocols were multi-center, multi-investigator studies, approved by institutional review board or independent ethics committee at each study center. Written informed consent was obtained from all participants.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More than 4,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Zika Test from Quest Diagnostics Authorized by the FDA
Company has announced that it has received a U.S. FDA emergency use authorization for the Zika Virus RT-PCR test.
Saturday, April 30, 2016
Quest Launches New Hep C Test
Quest Diagnostics has announced that it has expanded its chronic hepatitis C virus (HCV) test services to include new capabilities to help physicians identify or predict resistance to several HCV therapies.
Monday, April 18, 2016
Quest Diagnostics to Acquire Laboratory Outreach Service Business
Transaction to extend laboratory partnership serving patients and physicians in Southern California while bolstering Quest's growth strategy in the region.
Wednesday, July 01, 2015
Quest Diagnostics Named "Most Admired Company"
Company earns Fortune Magazine 2015 "World's Most Admired Companies" designation by Fortune Magazine.
Tuesday, February 24, 2015
Quest Diagnostics and CDC Expand Public Health Collaboration
Multi-year fee-based contract for Quest's test data and analytics expertise aims to reveal insights from national testing trends to promote guideline-based care and better outcomes for 4.4 million Americans with viral hepatitis.
Thursday, January 29, 2015
FDA Clears the Focus Diagnostics Simplexa™ Flu A/B & RSV Direct Test
Test kit with eight additional strains is now available directly in the United States.
Wednesday, December 10, 2014
Quest Diagnostics Adds Jeffrey M. Leiden to Board of Directors
Dr. Leiden has more than 20 years of scientific and commercial experience in the pharmaceutical and biotechnology industries.
Saturday, October 25, 2014
Quest Diagnostics Unveils New Clinical Laboratory in Marlborough, Massachusetts
Medical experts from UMass Memorial Medical Group and the University of Massachusetts to provide scientific leadership for testing onsite.
Tuesday, October 07, 2014
More People Testing Positive for Chikungunya Virus in the U.S.
Clinical testing volume and positivity rate both grew after the first case of the infectious disease spread to Western Hemisphere this year.
Friday, September 12, 2014
Quest Diagnostics Adds Vicky Gregg to Board of Directors
Company’s Board of Directors expand the Board to 10 members.
Friday, July 25, 2014
Quest Diagnostics Completes Acquisition of Summit Health
Summit's clients will access Quest's 2,200 patient service centers, biometric analysis.
Wednesday, April 23, 2014
Quest Diagnostics Elects Director
Quest Diagnostics announce that its Board of Directors has elected Timothy L. Main to serve as a director, effective immediately.
Tuesday, January 14, 2014
UC San Francisco and Quest Diagnostics Launch Collaboration
Collaboration to advance the field of precision medicine.
Friday, January 10, 2014
Quest Diagnostics Completes Acquisition of Clinical Outreach Operations of Dignity Health
Acquisition consistent with strategy to drive one to two percent in growth per year through strategically aligned fold-in acquisitions.
Friday, July 05, 2013
Quest Diagnostics Completes Sale of HemoCue Business to Radiometer Medical ApS
Company has completed the sale of its HemoCue diagnostic products business to Radiometer Medical ApS for a purchase price of approximately $300 million plus customary adjustments for cash balances.
Wednesday, April 10, 2013
Scientific News
Implementation Science Approaches to Reduce Mother-to-Child HIV Transmission
The NIH study will investigate best practices to ease major disease burden in Sub-Saharan Africa.
Portable Test Rapidly Detects Zika
To better diagnose and track the disease, scientists are now reporting a new $2 test that in the lab can accurately detect low levels of the virus in saliva.
New Nanoparticle Technology Developed to Treat Aggressive Thyroid Cancer
Researchers from Brigham and Women’s Hospital have developed a nanoplatform that can deliver RNAi agents to sites of anaplastic thyroid cancer.
Some Women With PCOS May Have Adrenal Disorder
Researchers at NIH have found that a subgroup of women with PCOS, a leading cause of infertility, may produce excess adrenal hormones.
Faster Detection of Pathogens in the Lungs
Thanks to new molecular-based methods, mycobacterial pathogens that cause pulmonary infections or tuberculosis can now be detected much more quickly.
Proteins in Blood of Heart Disease Patients May Predict Adverse Events
Nine-protein test shown superior to conventional assessments of risk.
£14m EU Project To Aid Meningitis Diagnosis and Cut Antibiotic Use
An international team of doctors are aiming to develop a rapid test to allow medics to quickly identify bacterial infection in children.
Bringing AFM to Medical Diagnostics
Company has announced that its NanoWizard® AFM and ForceRobot® systems are being used in the field of medical diagnostics in the Supersensitive Molecular Layer Laboratory of POSTECH in Korea.
Scientific Gains May Make Electronic Nose the Next Everyday Device
UT Dallas team breathes new life into possibilities by using CMOS integrated circuits technology.
Electronic Sensor Tells Dead Bacteria From Live
The sensor, which measures 'osmoregulation', is a potential future tool for medicine and food safety.
SELECTBIO

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!