Nucleic Acid-Amplification Testing Further Safeguards Nation's Blood Supply, NHLBI Study Shows
State-of-the-art testing systems to screen donated blood have improved
the safety of the nation’s blood supply by preventing the
transmission of potentially deadly viruses, according to a new study
funded by the National Heart, Lung, and Blood Institute (NHLBI),
a component of the National Institutes of Health. Nucleic acid-amplification
testing (NAT) has helped prevent the transmission of approximately
five HIV-1 infections and 56 hepatitis C virus (HCV) infections
each year since it began being used in the United States as an investigational
screening test in mid-1999. The study is published in the August
19 issue of the New England Journal of Medicine.
“Risks to blood recipients from transfusion-transmitted viruses
such as HIV and hepatitis are already extremely low, in part because
of increased surveillance and improved testing,” said Barbara
Alving, M.D., NHLBI acting director. “NAT enhances the safety
of the nation’s blood supply by further reducing these risks.”
The study is the first and only one of its scope to show the effectiveness
of the NAT assay system nationally. All major blood donation laboratories
in the United States participated, accounting for more than 98 percent
of tested blood donations. Many organizations collaborated on the
research, including the American Red Cross, Blood Systems Research
Institute, America’s Blood Centers, and the Food and Drug
The study investigators analyzed all donations that detected ribonucleic
acid (RNA) from HIV-1 and HCV by NAT between 1999 and 2002. The
researchers then looked to see which of these infected donations
had been missed by tests to detect viral antibodies or antigens
(proteins from the virus), the types of screening previously used.
They concluded that NAT reduced the risk of HIV-1 and HCV infections
associated with blood transfusion to approximately 1 in 2 million
blood units. In comparison, other blood screening tests are associated
with rates of 1 in 1.5 million for HIV-1 and 1 in 276,000 for HCV.
Blood donors have been tested for evidence of HIV infection since
1985 and for evidence of HCV infection since 1990. Although increasingly
sensitive tests to detect HIV and HCV antibodies and HIV antigen
were implemented during the past decade, in rare instances
infections in donors have been missed. This is due to the “window
period” during which a donor can be infected but still test
negative on screening tests.
The NAT system, which was approved for use in 2002 by the FDA,
can detect HIV and HCV infections in blood donors earlier than other
screening tests because it detects viral genes rather than antibodies
or antigens. The appearance of antibodies requires time for the
donor to develop an immune response, and detection of antigens requires
time for a higher level of virus to appear in the bloodstream.
With the use of NAT for HCV, the window period is reduced by approximately
60 days (from an average of 70 days to 10 days). For HIV-1, the
average window period with antibody is approximately 22 days. This
is reduced to approximately 11 days with the NAT tests used in this
study. The use of NAT has allowed blood banks to discontinue two
less effective screening tests HIV-1 antigen testing and
a test for a nonspecific marker for HCV. Blood donations continue
to be screened with antibody tests for HIV, HCV, and other viruses,
which helps ensure the safety of the blood supply.
“NAT not only improves the safety of our already safe blood
supply, but the technology can be quickly adapted to screen for
emerging viruses,” said George Nemo, Ph.D., project officer
of the study and group leader of the Transfusion Medicine and Cell
Therapies Scientific Research Group at NHLBI.
For example, last year, screening for West Nile virus was implemented
in less than nine months with the collaboration of the Centers for
Disease Control and Prevention and FDA and the rapid development
of NAT by manufacturers. Nearly 1,000 blood donors with West Nile
virus infection were identified by NAT and their donations discarded.
“These findings also reflect an unprecedented, national
cooperative effort by blood collection centers, industry, and federal
agencies, which greatly enhances the ability of blood donation centers
to rapidly incorporate new tests as needed,” added Nemo. “This
collaboration also facilitates our ability to conduct ongoing and
timely surveillance of the nation’s blood supply.”
NAT also makes it possible to identify persons in the very early
stages of HIV-1 and HCV infection. This information may help the
medical community better understand risk factors associated with
viral infection and the natural history, disease progression, and
treatment for these infections.
One of the NAT systems used in the study was first developed in
the mid-1990s by Gen-Probe Incorporated, in collaboration with Chiron
Corporation, with support for research and development provided
by NHLBI. Results of screening by the NAT system manufactured by
Roche Molecular Systems were also included in the study.
To interview Dr. Nemo about this study, please call the NHLBI Communications
Office at 301-496-4236.
NHLBI is part of the National Institutes of Health (NIH), the
Federal Government's primary agency for biomedical and behavioral
research. NIH is a component of the U.S. Department of Health and
Human Services. NHLBI press releases and fact sheets can be found
online at www.nhlbi.nih.gov.