Nucleic acid-amplification testing has improved the safety of the nation's blood supply

Aug 18 2004

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.

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 Administration (FDA).

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.