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454 Sequencing(TM) Identifies HIV Drug Resistance At Early Stage
454 Life Sciences, a member of
the Roche group, and a Yale School of Medicine researcher today announced
that they have used the company's Genome Sequencer(TM) system to identify
previously undetectable rare drug resistant HIV variants in samples from an
earlier performed clinical trial. The work, presented today by Michael
Kozal, M.D. of the Yale University School of Medicine and the VA CT Health
Care System, was a blinded-retrospective analysis of 258 blood samples
taken before drug treatment from HIV infected individuals. The results were
presented today at the XVI International HIV Drug Resistance Workshop in
Barbados and showed that the fraction of patients that harbored resistance
mutations is at least twice as high as previously thought. Most low level
mutations are undetectable by current resistance testing methods that are
used in the clinic. The additional low abundant resistant variants detected
by Ultra Deep sequencing were found to be extremely important as it enabled
the prediction of early antiretroviral treatment failure with strong
statistical significance.
"Current genotypic resistance technology available to clinicians is
limited to detecting resistance mutations that are present at levels of
approximately 20% or greater in the circulating viral population in a
patient. Thus, the current technology used in the clinic may miss many
low-level resistant HIV strains which can grow rapidly under drug selection
pressure and lead to therapy failure. This retrospective study clearly
shows that even resistance mutations present at the 1% level lead to
premature failure of therapy" explained Michael Kozal, M.D. the senior
author on the study. "In the future, hopefully clinicians can use this
knowledge to choose better antiretroviral drug combinations that have the
ability to suppress these resistant HIV strains which will lead to better
clinical responses in patients."
While treatment of HIV has been largely successful, with dramatic
increases in survival over the last decade, a significant number of
patients develop drug resistance shortly after treatment is initiated. The
collaboration between 454 Life Sciences and Yale University aimed to
determine if patients that fail therapy early were initially infected with
a drug resistant HIV strain or if mutations arose in response to treatment.
This research project examined samples from 258 subjects of the FIRST
study, a large multi-center study conducted in the US comparing three
different approaches to antiretroviral therapy. The FIRST study, which
lasted 5 years, evaluated the long-term clinical and virologic effects of
three initial antiretroviral drug regimens for treatment naive HIV-infected
persons. The CPCRA Statistical Center at the University of Minnesota
correlated the sequence data with the patient outcomes, to which 454 Life
Sciences was blinded.
"454 Sequencing can instantly generate hundreds of thousands of long
clonal sequence reads that accurately enable the sensitive detection of
rare mutations" explained Egholm Michael, Ph.D. vice president of research
and development at 454 Life Sciences. "Ultra Deep Sequencing provides an
essential tool for research on viral diseases and their treatments. The
ability to use 454 Sequencing to detect rare viral mutations is a crucial
research tool to better understand the early stages of HIV drug
resistance."
It is estimated that 22 million people have died from AIDS and over 42
million people are living with HIV/AIDS worldwide. In the U.S. alone,
40,000 new infections occur each year.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's
leading research-focused healthcare groups in the fields of pharmaceuticals
and diagnostics. As the world's biggest biotech company and an innovator of
products and services for the early detection, prevention, diagnosis and
treatment of diseases, the Group contributes on a broad range of fronts to
improving people's health and quality of life. Roche is the world leader in
in-vitro diagnostics and drugs for cancer and transplantation, a market
leader in virology and active in other major therapeutic areas such as
autoimmune diseases, inflammation, metabolism and central nervous system.
In 2006 sales by the Pharmaceuticals Division totaled 33.3 billion Swiss
francs, and the Diagnostics Division posted sales of 8.7 billion Swiss
francs. Roche employs roughly 75,000 worldwide and has R&D agreements and
strategic alliances with numerous partners, including majority ownership
interests in Genentech and Chugai. Roche's Diagnostics Division offers a
uniquely broad product portfolio and supplies a wide array of innovative
testing products and services to researchers, physicians, patients,
hospitals and laboratories world-wide. For further information, please
visit our website at http://www.roche.com.
About 454
454 Life Sciences Corporation develops and commercializes novel
instrumentation for high-throughput DNA sequencing. Specific applications
include whole-genome sequencing, RNA analysis and ultra-deep sequencing of
target genes. The hallmarks of 454 Sequencing(TM) are its simple, unbiased
sample preparation and massively parallel sequencing, which makes
large-scale scientific projects feasible and more affordable. 454
Sequencing and the Genome Sequencer 20 System won The Wall Street Journal's
top Innovation Award in 2005 and received an R&D 100 Editor's Choice Award
as one of the most technologically significant products in 2006. The 454
Sequencing Center offers sequencing services directly to customers on a fee
for service basis. Genome Sequencer systems are distributed by Roche
Applied Science. 454 Life Sciences is a business unit of Roche Applied
Science, a division of Roche Diagnostics. For additional information,
please visit http://www.454.com.
454 Life Sciences
http://www.454.com
454 secvenþiere (tm) identificã cu HIV de droguri de rezistenþã la stadiu incipient - 454 Sequencing(TM) Identifies HIV Drug Resistance At Early Stage - articole medicale engleza - startsanatate