MBE - Abbott Laboratories' HIVAG-1 test (10/4/89)

DATE:      October 4, 1989

FROM:      Director, Center for Biologics Evaluation and Research

SUBJECT:   Abbott Laboratories' HIVAG-1 test for HIV-1 antigen(s)
           not recommended for use as a donor screen.

TO:        All Registered Blood Establishments


On August 3, 1989, the Food and Drug Administration licensed
Abbott Laboratories, North Chicago, Illinois, to manufacture and
distribute an enzyme-linked immunoassay for the qualitative,
in-vitro, detection of HIV-1 antigen(s) in human serum or plasma.
The test is called HIVAG-1. As stated in the package insert, "It
is intended to be used as an aid in the diagnosis and prognosis
of patients with HIV-1 infection." The label does not include an
indication for donor screening.

The FDA does not recommend the use of this test for screening of
donations of either whole blood or source plasma. The purpose of
this memorandum is to declare this position, and explain its
rationale.

The indications for licensure of Abbott's antigen test were
discussed at a public meeting of the Blood Products Advisory
Committee on March 23, 1989 in Bethesda, Maryland. At this
meeting the FDA received endorsement of its positions: a) that
screening of source plasma would not add significantly to the
safety of plasma derivatives, b) that screening of whole blood
would not add measurably to the safety of the blood supply, and
c) that the test has value for prognosis and other clinical
diagnostic uses. The arguments can be summarized as follows:

     a)   argument against screening of source plasma donations

     Although a study conducted by Abbott Laboratories (S.
     L. Straemer, et al., JAMA 1989; 262:64-69)
     demonstrated the presence of HIV antigen prior to
     antibody in four out of seven source plasma donors
     who seroconverted and had samples stored from
     previous donations, there is overwhelming evidence
     that plasma derivatives no longer transmit HIV. Thus,
     the antigen test is unnecessary for screening of
     plasma intended for further manufacture into
     derivatives.

     b)   argument against screening of whole blood donations

     The efficacy of the antigen test for "early"
     detection of HIV-1 infection prior to seroconversion
     in donors of whole blood has been examined in Europe
     and the United States.  Studies in West Germany and
     Austria failed to reveal a single case of "early" HIV
     detection in approximately 595,000 screened donations
     between March 1987 and April, 1988. In the United
     States, a study of over 200,000 (now updated to
     exceed 500,000) whole blood donors screened
     since January, 1989 was also negative. In addition,
     retrospective testing of the repository of the
     Transfusion Safety Study failed to reveal a case
     positive for HIV antigen and negative for HIV
     antibody among 2,292 samples from male donors in
     areas of high antibody prevalence who were drawn
     between September 1984 to February, 1985.
     Collectively, these studies show that detection of
     antigen without antibody is rare event in the whole
     blood donor population (less than one per million).
     Thus, routine use of the antigen test would not add
     significantly to the safety of the blood supply, even
     though a person with recent HIV infection could
     donate prior to the development of antibodies.

     c)   licensure as a clinical diagnostic test

     The FDA accepted the data of Abbott Laboratories
     which indicated efficacy of the HIVAG-1 test for
     early diagnosis of HIV-1 infection in individuals at
     high risk, and as a prognostic test to estimate the
     risk of progression to ARC or AIDS in asymptomatic,
     seropositive persons. The test was therefore licensed
     for its diagnostic and prognostic use.

A similar recommendation against antigen testing of blood donors
was publicized by a Select Committee of Experts of the Council of
Europe which met in March, 1989 in Innsbruck, Austria. That
group stated that "currently available HIV-antigen tests will not
add to the security gained by screening of donors with current
anti-HIV-1 tests, though the danger of HIV transmission by
donations taken before seroconversion still exists."

                             
                             Paul D. Parkman, M.D.