BERKELEY, CA -- October 28, 1997: New research shows that a combination of urine and blood-based tests can detect antibodies to the human immunodeficiency virus, type 1 (HIV-1) with greater sensitivity than can be achieved by either test alone. Results of clinical trials reported by researchers from Calypte Biomedical Corporation (Nasdaq: CALY) in the November issue of Nature Medicine showed that some individuals who test positive for antibodies to HIV-1, the virus associated with acquired immunodeficiency syndrome (AIDS), may produce such antibodies in one body fluid but not another. Moreover, in a second publication in the same journal, researchers from the University of Milan found that individuals demonstrating a strong natural immune response to the HIV-1 virus produce antibodies in urine and vaginal samples, but not in blood, thus potentially simplifying the identification of HIV-resistant individuals.
In order to evaluate the performance of Calypte's urine test for HIV-1 antibodies against conventional blood-based HIV tests, company researchers conducted a large clinical trial with over 22,000 samples tested at 11 independent laboratories. To resolve discrepancies where a person's blood test did not agree with their urine test, the researchers additionally tested both sample types by a confirmation test, the Western Blot. Out of 1,181 subjects who tested HIV-1 positive by Western Blot, the researchers found 25 discordant samples (samples showing discrepant test results): 10 in which antibodies were detected by the urine test alone and 15 where antibodies were detected by the blood test alone. The publication's authors concluded that combination sampling with at least two body fluids could identify more HIV-infected and exposed individuals than the use of either test alone.
Howard Urnovitz, Ph.D., study co-author and chief science officer at Calypte Biomedical said, "The detection of HIV-1 discordant samples is not that surprising. As early as 1990, studies have shown that individuals can be antibody positive in one body fluid but negative in another. Every individual's immune system responds differently to viral infections. This study suggests that a small, but significant, percentage of individuals appear to confine the HIV-1 infection to a limited number of tissues and organs, a process called 'compartmentalization'."
Dr. Alvin Friedman-Kien, professor of microbiology and dermatology at New York University Medical Center, who first discovered HIV-1 antibodies in urine, said, "This breakthrough in diagnostic research is analogous to recent therapeutic advances in AIDS treatment where combination therapy has replaced monotherapy." Dr. Friedman-Kien is a member of Calypte's scientific advisory board.
Several implications arise from studying people who exhibit discordant samples. First, combination urine and blood testing could lead to more sensitive detection of HIV-1 antibodies. Second, such testing would facilitate the identification of individuals with either a compartmentalized HIV-1 infection or a compartmentalized immune response to HIV-1. Finally, understanding the mechanism behind such compartmentalized responses could provide new directions in research for the development of a safe and effective AIDS vaccine.
In a companion study published in the same issue of Nature Medicine, Mario Clerici, M.D. of the University of Milan, Italy, and his colleagues used a modification of the Calypte urine test to study 16 heterosexual individuals who tested positive for HIV-1 antibodies in their blood (seropositive) and their HIV-1-exposed, seronegative partners. The researchers found HIV-1 specific IgG and IgA antibodies in the HIV-1 seropositive individuals' blood, urine and vaginal swabs. The seronegative partners had no IgG antibodies, but exhibited strong IgA anti-HIV-1 responses in their vaginal and urine samples. These seronegative partners also tested positive for a cellular immune response to parts of the HIV-1 envelope, indicating that they had indeed been exposed to the virus.
Dr. Clerici, with colleague Gene Shearer, Ph.D. of the National Cancer Institute, USA, has reported for several years on individuals who demonstrate a strong cellular immune response to the HIV-1 virus. This type of immune response may prevent HIV-1 exposed individuals from seroconverting (developing antibodies in the blood) and developing disease.
Dr. Shearer said, "When it comes to questioning whether there is a protective immune response against HIV infection, we believe that nature has already done the experiment for us. These findings of IgA antibodies with a simple, inexpensive urine test moves us one step closer to doing epidemiology studies to determine how many people exhibit this type of immunity to HIV."
Professor Luc Montagnier, the discoverer of HIV-1 and a member of Calypte's scientific advisory board, commented, "The possibility of identifying naturally immune people gives us more directions to pursue for a successful treatment against the AIDS virus. We need to focus our resources on how to translate these findings of natural immunity into safe and effective vaccines."
Calypte Biomedical Corporation is an Alameda and Berkeley, California-based health care company dedicated to the development and commercialization of urine-based diagnostic products and services for HIV-1, sexually transmitted diseases and other chronic illnesses.