Use of the Recombigen HIV-1 LA Test (2/1/89)

Date :      February 1, 1989

From :      Director, Center for Biologics Evaluation and
            Research

Subject:    Use of the Recombigen HIV-1 LA Test

To:         All Register Blood and Plasma Establishment

On December 13, 1988, the Food and Drug Administration licensed
Cambridge Bioscience Corporation, Worcester, MA to manufacture
and distribute a rapid latex agglutination screening test for
antibodies to HIV-1 called "Recombigen" HIV-1 LA Test." The
test is labeled for use "by properly trained personnel as a
screening test in hospital laboratories, medical clinics,
physicians' offices, and emergency care situations, and in blood
banks or other settings where enzyme immunoassays are not
practical or available." The purpose of this letter is to
clarify FDA's concept of the appropriate use of this test in
blood and plasma establishments.

The latex agglutination test can be performed in as little as
five minutes with a sample of venous or capillary whole blood,
serum or plasma which is diluted on a card and then mixed-with a
suspension of microscopic latex particles which have been coated
with a recombinant DNA-derived protein related to the virus
envelope. The test endpoint is determined by visual inspection
for an agglutination reaction in comparison with a negative
control. As documented in the package insert, this test, when
properly performed, is at least as sensitive as the licensed EIA
screening tests.

Several clinical studies have shown that the Recombigen test may
frequently give rise to false positive results. The primary
cause of this problem is that the agglutination reaction can be
easily overinterpreted by inexperienced operators. For this
reason, the manufacturer requires that users familiarize
themselves with the test by the use of a training panel and an
"Interpretation Guide." In addition, the test can be falsely .
positive in a variety of medical conditions including common
viral infections and the presence of certain abnormal serum
immune globulins. Also, the format of the test, which lacks
automated procedures and objective read-out, may dispose to
errors inherent with tests that utilize subjective reading and
interpretation.

The particle agglutination test is not recommended for routine
use in registered blood and plasma collection establishments
because of the procedural difficulties and hence errors that
would be likely to arise in handling large numbers of samples and
because of the likelihood of false positive tests. Users of the
test should be aware that donors with repeatably reactive tests
by this procedure should be counseled and permanently excluded
from donating blood or plasma unless they can be requalified by
the reentry algorithm defined in a letter of April 29, 1987. In
the event that a donor is deferred on the basis of the latex
agglutination test, the latex test should be read in place of the
initial EIA or "iEIA" mentioned in the document on reentry.
Since the latex test uses a purified and genetically engineered
polypeptide related to the viral envelope protein, the different
screening test referred to in the algorithm as "dEIA" may be a
test based on virus cultured in either the H-9 or the CEM cell
line.

As is the case for other licensed screening tests for antibodies
to HIV, it is recommended that additional more specific tests
such as Western blot be performed prior to notification of donors
who have been deferred. It is not appropriate to "validate" the
results of the latex agglutination test with other licensed
screening tests prior to notification. Also, it is not
appropriate to "re-screen" donors previously positive by the
latex agglutination test with licensed EIA tests prior to
distributing units for transfusion or further manufacture.
Routine "pre-screening" of donors such as on mobile collection
facilities would not be a valid use since that practice would be
likely to generate a large number of false-positive tests leading
to excessive donor exclusion and further testing.

Medical discretion should be used to decide whether the latex
agglutination test is indicated in a particular instance because
screening by the EIA is impractical or unavailable. Emergency
situations involving donations of rare blood types, or urgent
management of disasters might be examples. It is expected that
the test will be used as the primary blood screen in some
developing countries. It should be noted by such users that the
manufacturer has made no claim for test sensitivity for detection
of antibodies to HIV-2.


                          Paul D. Parkman, M.D.
                          Director
                          Center for Biologics
                           Evaluation and Research