a report by
C a l y p t e B i o m e d i c a l C o r p o r a t i o n
Calypte Biomedical Corporation has been involved
in the pursuit of novel infectious disease diagnostics
for over a decade. Not content with simply making
Calypte versions of tests that are readily available
from a variety of suppliers, Calypte’s focus is on
developing, manufacturing and distributing tests that
other companies do not or cannot, with a particular
focus on HIV.
Calypte may be best known as the only company to
have developed and achieved US Food and Drug
Administration (FDA) approval for a urine screening
enzyme-linked immunosorbent assay (ELISA) for
HIV-1 antibodies, as well as its corresponding
Western Blot.
The development of HIV antibody assays, which use
non-blood samples, remains a passion of the
company. It is currently launching three rapid tests
for HIV-1/2 antibody, including a rapid urine test
and a rapid oral fluid test.
T h e C a s e f o r A l t e r n a t i v e S a m p l e s
There is broad consensus that testing, coupled with
counselling, is a fundamental and critical aspect to
HIV control. With a few exceptions, such testing
and counselling is voluntary, so the success of such
efforts depends largely on the willingness of the
public to participate; however, for a variety of
reasons, the public may not participate in the
numbers desired. Knowing, for example, that HIV
testing is typically performed on blood samples, the
public may opt out of testing – even if they know
they may be at risk – due to fears of pain and safety,
or for cultural reasons.
The ability to perform HIV testing accurately and
safely using both urine or oral fluid samples has been
amply documented, as has the increase in voluntary
testing rates when such alternatives are offered.
T h e C a s e f o r R a p i d H I V
A n t i b o d y T e s t i n g
Rapid, point-of-care (POC) testing for HIV
antibody is appropriate in a variety of settings. It has
been widely noted that substantial numbers of
people who participate in voluntary testing and
counselling programmes and provide samples for
testing, never return for their results. Whether this
occurs due to fear of the outcome, inconvenience
or other reasons, the result is that HIV-infected
people remain undiagnosed and untreated. In the
developing world where the HIV epidemic is most
acute, rapid testing algorithms using multiple rapid
tests in series or parallel have become
commonplace. In addition to the benefit of
immediate referral to treatment, rapid tests can be
performed in the absence of properly equipped
laboratories or skilled laboratorians.
Aware™ Rapid HIV Antibody
T e s t i n g w i t h A l t e r n a t e F l u i d s
Calypte’s Aware rapid tests have been designed with
the developing world in mind. Available only in
selected markets, the tests have been designed to offer
optimal accuracy, economy and patient appeal. The
assay test strip is in a dipstick format that is more
economical to manufacture and less expensive for
disposal. Patients are familiar with the dipstick format
from participating in routine urinalysis.
By combining the proven benefits of alternate fluid
sampling with the proven benefits of rapid testing,
Calypte believes that it offers a broader range of rapid
testing options than any other company.
A w a r e T e s t s
Three Aware tests have been developed:
• Aware BSP for use with whole blood, serum,
and plasma;
• Aware OMT for use with oral mucosal transudate
(oral fluid); and
• Aware U for use with urine samples
All three tests are sensitive to both HIV-1 and
HIV-2. Calypte is a duly licensed manufacturer of
HIV-2 rapid tests, so there is no risk that
production will be interrupted in the future for
reasons of HIV-2 patent infringement.
Calypte Biomedical Corporation –
Innovators in Infectious Disease Testing
1.B U S I N E S S B R I E F I N G : E U R O P E A N P H A R M A C O T H E R A P Y 2 0 06
Technology & Services Section
2.B U S I N E S S B R I E F I N G : E U R O P E A N P H A R M A C O T H E R A P Y 2 0 0 6
Each of the three tests takes 20 minutes to perform,
and include a true human immunoglobulin G (IgG)
control line that verifies both that the test device is
working properly and that the appropriate sample
was introduced to the device.
Each of the three tests is sold in kits of 25 or 50 tests
and can be stored and shipped without refrigeration.
Two of the Aware tests (BSP and OMT) require the
use of a buffer solution and this is provided in excess.
The kits include multiple buffer droppers so that
multiple users can use the same test kit
simultaneously. The rapid urine test requires no
buffers or sample preparation – simply drop a dipstick
into a tube containing urine.
S p e c i a l i t y P r o d u c t s f o r
H I V E p i d e m i o l o g y
The use of widely available HIV antibody tests can
provide useful information about HIV prevalence in
a given population at a given point in time.
However, one of the most vexing problems for HIV
researchers has been the estimation of HIV incidence
– the number of newly acquired infections. Clearly,
two populations with identical prevalence at some
point in time can have dramatically different
incidence rates – one group may be experiencing a
steady or declining rate of new infections while the
other may be experiencing explosive growth.
An understanding of HIV incidence trends is critical
for many people engaged in HIV control efforts.
Policy makers, financial and resource planners and
programme managers all need to understand the
nature and scope of the HIV epidemic in populations
if they hope to intervene in a timely manner, plan for
the future and determine which programmes are
working and which are not.
Past efforts to estimate HIV incidence have been
based on assay ‘detuning’, whereby highly diluted
samples are run on a commercially available HIV-1
enzyme immunoassay (EIA) test, with the
expectation that only those sera associated with longestablished
infections will have a high enough titre to
yield a reactive result. This approach is prone to
reproducibility problems and a sensitivity that is
limited to a small range of HIV subtypes.
The HIV-1 BED Incidence EIA is a microwell EIA
test for use with serum or plasma samples previously
determined to be reactive for HIV antibody.
Originally developed by the US Centers for Disease
Control (CDC), Calypte was licensed to
commercialise the test in 2004. The assay is intended
for surveillance purposes only, to estimate HIV-1
incidence in populations. Since it is not used in the
diagnosis or treatment of individual patients, most
countries permit the import and use of this product
without official registration.
The assay is based on the observation that
following infection, the ratio of HIV-specific
IgG:Total IgG ratio continues to rise. This EIA is
quantitative and includes the standards needed to
validate the assay. A calibrator is also provided that
performs in the assay at the typical HIV-specific
IgG:Total IgG ratio found 5.5 months postinfection
and is used to provide a threshold cutoff
for the classification of recent seroconversion.
Samples with optical densities (ODs) below this
threshold are presumptively considered ‘recent’
and must be repeated in triplicate. The reference in
the product’s name to BED relates to the use of a
unique branched multi-subtype gp41 peptide that
incorporates the immunodominant regions from
subtypes B, E and D. This confers upon the assay
with equal sensitivity across types A–F.
F u t u r e D e v e l o p m e n t s i n
I n c i d e n c e T e s t i n g
In collaboration with the US CDC, Calypte is
developing an application that will permit the BED
Incidence EIA to be used with dried blood spots
(DBS) or dried serum spots (DSS) – a development
that will expand the utility and convenience of the
assay. Dried blood and serum samples are easy to
collect and store and the blood spot application for
BED would permit retrospective analysis of
archived samples that have been collected in this
manner. In addition, routine collection of such
samples can be conveniently integrated into HIV
screening programmes in such a way that blood spot
samples associated with positive HIV antibody
screening results can be set aside for subsequent
incidence testing.
The dried blood spot application for the HIV-1 BED
Incidence EIA will entail the use of an accessory pack
of controls and standards in DBS format, which is
used along with the regular BED test kit.
Commercial availability of the accessory pack is
anticipated late in 2005. ■
http://www.touchbriefings.com/cdps/cditem.cfm?cid=5&nid=1890
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