Research Findings Point To Need For HIV Testing With Both Blood And Urine
LENEXA, Kan.--Dec. 3, 1998--Clinical Reference Laboratory (CRL), one of the country's leading
clinical reference laboratories, announced today results of the
largest study to date showing a significant proportion of individuals
- approximately one out of every 1,000- within the low risk population
test positive for HIV-1 antibodies in their urine and negative in
their blood.
Dr. Robert Stout, president of CRL, said, "Test results from two
body fluids that do not agree are referred to as 'discordant.' This is
the first time we have found HIV-1 discordant results in a large, low
risk group using an FDA- licensed urine screening test. The
significance of this report is twofold. First, the results suggest
that people being tested for HIV antibody should have both their blood
and urine screened. Second, the presence of antibody against HIV-1 in
the urine indicates, at the very least, a prior exposure to the
virus."
The CRL study tested matched blood and urine samples from over
50,000 individuals at low risk for contracting HIV-1 infection. All
study subjects had signed consent forms to be tested for HIV-1. The
study found 19 out of 50,231 individuals (0.038% or approximately 1
out of every 3,000 Americans) were blood positive for HIV-1, an
incidence consistent with the percentage found in the general
population within the U.S. The urine test identified 17 out of 18
seropositives identified in the study (one matched urine sample from a
seropositive individual could not be tested). In a subgroup of 25,106
individuals, 24 samples were negative by blood tests but positive by a
FDA- licensed urine HIV-1 antibody screening test manufactured by
Calypte Biomedical Corporation.
An investigational new test showed that the 24 discordant
urine-only reactive samples were repeatedly reactive for a particular
type of HIV antibody made mostly in the mucosal tissues, i.e.
Immunoglobulin A antibody, also called IgA. The mucosal tissues are
the protective linings in the body's many cavities, including the
urogenital tract. The antibody was specific for HIV-1 but not for
other retroviruses tested. The occurrence of urine IgA HIV antibodies
was 0.096% or 2.5 times more frequent than that of the blood positive
frequency. In low risk populations, HIV is most often first
encountered by the mucosal tissues during sexual activity. Presence of
this antibody indicates that, at the very least, the individual has
been exposed to HIV-1.
R. Scott Hitt, MD, Chairman, The Presidential Advisory Council on
HIV/AIDS, said, "Clearly, these results point to the need for
extensive studies that can further support the discordancy factor in
screening of individuals for HIV-1. Increased prevention efforts for
HIV infection must include more accurate means for determination of
those in all risk categories who have been exposed to the virus, and
it should be the responsibility of public health officials to
undertake every avenue to ensure that an individual at risk for HIV
knows his or her status. Only by this process of earlier and accurate
screening can we provide the best possible treatment therapies."
"Discordant HIV-1 antibody tests are an important public health
issue," said Dr. Roy Stevens, former director of the New York State
Department of Health Laboratories for Retrovirology/Immunology and
chairman of the Clinical Immunology Division of the American Society
for Microbiology from 1997 to 1998. "I support the concept of
combination testing using both serum and urine to increase the
sensitivity of HIV-1 antibody testing. Combination testing would help
meet one of the objectives of the Center for Disease Control and
Prevention's Laboratory Initiatives For The Year 2000 which calls for
new testing technologies for greater risk reduction."
"The CRL study is very significant," stated Mario Clerici, M.D.,
associate professor at the University of Milan, and discoverer of
HIV-1 IgA in the mucosal tissues of blood negative individuals. "My
research has shown that some high risk blood negative persons
continually exposed to HIV-1 positive sexual partners are known to
have IgA only HIV-1 antibodies in their urine. The CRL study is the
first large study to look at and conclude similar findings in the low
risk population. These urine-only HIV-1 antibody-positive subjects are
critical to helping us understand why some people's immune systems can
keep HIV-1 contained and silent within certain body compartments. The
answer to this question is fundamental to the development of any
vaccine or immune based therapeutic."
Scientists believe that the reason some persons show antibodies
in their urine, but not in their blood is based on their ability to
"compartmentalize" the virus, (i.e., the HIV virus is contained to
specific body tissues).
The CRL data are consistent with the compartmentalization of HIV,
a hypotheses first proposed by Dr. Ann Kiessling of Beth Israel
Deaconess Medical Center, Harvard Medical School. Dr. Kiessling's
hypothesis raises the question that if the virus is compartmentalized,
as the data for the low risk population suggest, how is the individual
able to avoid more general infection of the blood? The study of urine
and serum discordant patients may provide additional insight into the
genetic and/or environmental factors that protect some people from a
disseminated infection. Dr. Kiessling said, "There is a very important
aspect of HIV-1 infection that has been overlooked. The virus can
isolate itself and reproduce in tissues away from the blood. When this
happens, it is not surprising that specific antibodies would be found
in tissue fluids that are not detected in standard blood assays."
Professor Luc Montagnier, co-discoverer of HIV-1, chaired a
meeting in Geneva earlier this year at the 1998 12th World AIDS
Conference that focused on discordancy and compartmentalization.
Professor Montagnier said, "It was known that some individuals who are
at high risk for HIV could remain seronegative, while showing local
immune response in their urogenital tract. In view of similar
discordancies found in the CRL low-risk population study, we need to
do more research and larger epidemiologic studies to evaluate the
significance of this new finding.
The CRL study was co-sponsored by CRL and the manufacturer of the
urine test kit, Calypte Biomedical Corporation, Berkeley, CA. Several
other studies during the last six years have also revealed such
discordant findings in smaller sample sizes. However, the earlier
studies were conducted among groups of individuals that were at high
risk for HIV-1 infection.
Dr. Stout added that, "Since the presence of urine IgA antibody
to HIV indicates an exposure, the major implications of these findings
include 1) Was the HIV infection successfully aborted by mucosal
immunity? or 2) When the HIV infection occurred, was it restricted or
compartmentalized to tissue or organs of the urogenital tract in some
individuals? The study of individuals that have been able to
recognize, compartmentalize, or eliminate the virus may prove very
useful for the development of vaccine candidates. The significance of
these findings, for the understanding of the natural history of
infection by HIV-1, will require additional studies."