A NEW BLOOD DONOR SCREENING TEST TO FURTHER IMPROVE BLOOD SAFETY: HIV-1 P24 ANTIGEN

Introduction:

Sometime during the next several weeks, the Food and Drug Administration (FDA) will license a test for HIV-1 p24 antigen to be used in screening the nation’s blood supply. This assay directly detects the presence of HIV-1 antigen (HIV-1 Ag) in blood and appears as early as 6 days before the current screening test, HIV-1/HIV-2 antibody, becomes positive. HIV-1 Ag screening used in conjunction with HIV antibody testing will detect some seronegative infectious donors before they seroconvert, thereby reducing the residual risk of HIV in the blood supply.

Background:

In March 1989, the Blood Products Advisory Committee (BPAC) of the FDA recommended licensure of a test for the detection of HIV-1 Ag(s) in serum or plasma for diagnosis and prognosis of patients with HIV-1 infection, but not as a screening test for blood and plasma donors. This decision was based on the lack of detection of antigen positive, antibody-negative donations in large scale donor screening studies conducted both in the United States and Europe, involving over 1 million donors. These and other studies suggested that detection of HIV-1 Ag in the absence of antibody would be a very rare event in U.S. donor screening, although the frequency of detection could not be estimated.

Recently, the role of HIV-1 Ag testing of blood donors has been reconsidered because of: (1) four documented instances of HIV-1 transmission by HIV-1 Ag positive donations from three HIV-1 antibody negative donors, and (2) recent estimates of the residual risk of HIV transmission by screened blood and the efficacy of antigen screening to detect seronegative, infectious donations. The antibody- negative infectious "window period" is approximately 22-25 days for screening with combination assays for antibodies to HIV-1 and HIV-2. Virtually all present-day transfusion-transmitted HIV risk results from donations within this window period. Therefore, reducing this interval by six days through donor screening using HIV-1 antigen will prevent up to 25% of current "window period" cases, or about 5-10 infections of transfusion-associated HIV per year in the United States. In Pittsburgh, the overall benefit in terms of blood safety would be to make the already low risk of HIV even lower, i.e., the current estimated risk of 1 in 960,000 would improve to about 1 in 1.2 million per unit (or one potential case per six years). Overall, this represents remarkable progress in transfusion safety in comparison to risk levels of a decade ago.

Implementation:

In August 1995, the FDA issued recommendations on donor screening for HIV-1 Ag in advance of the availability of such tests in order to provide blood and plasma establishments with maximum time to prepare for this testing. It should be noted that the decision to require the HIV-1 Ag test has not been without controversy, considering its substantial cost (estimated at 60 to 100 million dollars annually) and the small increment in blood safety that will be realized.

In response to the FDA requirement, Central Blood Bank (CBB) has developed a comprehensive implementation plan and will begin testing once licensure has been granted. While not mandated by the FDA, the inventory of all blood collected within 42 days prior to test licensure will be "back-tested". This is being done to ensure the uniform safety of the entire region’s blood supply as expeditiously as possible after the test is released. Although the net impact of the HIV-1 Ag test on the risk of HIV from a blood transfusion in our region will be very small, some physicians may want to consider the potential improvement in blood safety in the scheduling of elective surgery likely to require allogeneic blood products, and for non-urgent transfusions. In this regard, we anticipate that the regional blood inventory will be fully tested within 4 to 5 days of licensure.

Test Interpretation:

HIV-1 Ag is measured by enzyme immuno-assay (EIA). Repeatedly reactive specimens are subjected to a neutralization test. A positive neutralization test result indicates the presence of HIV-1 antigen. Donor samples which are repeatedly reactive in the screening EIA, but which are negative in the neutralization assay are unlikely to contain HIV-1 antigen. However, because of the possible occurrence of false negative neutralization tests, they are classified as indeterminate. A follow-up sample from the donor at least eight weeks later, tested for HIV-1/2 antibodies, is required to definitively diagnose or exclude infection.

Policies:

In accordance with FDA directives, all allogeneic as well as autologous units which test HIV-1 Ag repeat reactive in the screening test will be discarded. Hospital transfusion services will be notified to quarantine and return to the blood center in-date units collected within a three month period prior to a donor’s current repeatedly reactive screening test for HIV-1 Ag. Neutralization test results will be conveyed if such units have been transfused. Recipient tracing (lookback) and notification to the attending physicians should be done by the transfusion service for transfused components with positive HIV-1 Ag neutralization results. If the neutralization test is indeterminate, however, a judgement by the Transfusion Service Medical Director should be made regarding the potential benefits of recipient tracing prior to resolution of the HIV status of the donor through follow-up HIV antibody testing. The Institute’s Medical Staff are available to provide guidance, should these challenging notification issues arise.

For questions or comments about HIV-Ag testing, please contact
Joseph E. Kiss, M.D. at (412) 209-7326.

Copies of the Transfusion Medicine Update can be obtained by contacting
Deborah Small at (412) 209-7320