Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

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:

"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
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 2,600+ scientific posters on ePosters
  • More Than 3,800+ 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 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

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
Quest Diagnostics Names Sukumar Nagendran, M.D., Vice President, Medical Affairs
In this role, Dr. Nagendran will provide medical oversight for the company's diagnostic information services.
Thursday, April 04, 2013
Prescription Drug Misuse Remains at Alarming Levels
Quest Diagnostics Health Trends™ analysis of a quarter million test results finds three out of five Americans tested misused their prescription medications.
Thursday, April 04, 2013
Scientific News
Lung Repair and Regeneration Gene Discovered
New role for hedgehog gene offers better understanding of lung disease.
How Cell Growth Triggers Cell Division
Researchers in Jan Skotheim's lab have discovered a previously unknown mechanism that controls how large cells grow, an insight that could one day provide insight into attacking diseases such as cancer.
Microbe Sleuth
Tanja Bosak examines how life and the Earth evolved in tandem during their early history together.
3 Ways Viruses Have Changed Science for the Better
Viruses are really good at what they do, and we’ve been able to harness their skills to learn about – and potentially improve – human health in several ways.
Restoring Vision with Stem Cells
Age-related macular degeneration (AMRD) could be treated by transplanting photoreceptors produced by the directed differentiation of stem cells, thanks to findings published today by Professor Gilbert Bernier of the University of Montreal and its affiliated Maisonneuve-Rosemont Hospital.
The Age of Humans Controlling Microbes
Engineered bacteria could soon be used to detect environmental toxins, treat diseases, and sustainably produce chemicals and fuels.
Mixed Up Cell Transportation Key Piece of ALS and Dementia Puzzle
Researchers from the University of Toronto are one step closer to solving this incredibly complex puzzle, offering hope for treatment.
Metabolomic Platform Reveals Fundamental Flaw in Common Lab Technology
A new study led by scientists at The Scripps Research Institute (TSRI) shows that a technology used in thousands of laboratories, called gas chromatography mass spectrometry (GC-MS), fundamentally alters the samples it analyzes.
Atriva Therapeutics GmbH Develops Innovative Flu Drug
Highly effective against seasonal and pandemic influenza.
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos