Major New Study Shows HIV-1 Antibodies Found In Urine

December 03, 1998

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."



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