This contract program developed and evaluated procedures used in screening and monitoring the infectivity of people who are carriers of HIV-1.
Seven contracts were supported and two were extended to complete promising work. The program ended in 1992.
N01 HB67017 - Robert Yolken - Johns Hopkins University, Baltimore, MD
N01 HB67019 - Douglas Richman - University of California, San Diego, CA
N01 HB67020 - Girish Vyas - University of California, San Francisco, CA
N01 HB67021 - Bernard Poiesz - State University of New York, Stony Brook, NY
N01 HB67022 - Robert Singer - University of Massachusetts, Boston, MA
N01 HB67023 - Betsy Ohlssen-Wilhelm - Hershey Medical Center, Philadelphia, PA
N01 HB67024 - Girish Vyas - University of California, San Francisco, CA
Dr. Vyas used flow cytometry to detect the presence of antibody to HIV. After polystyrene beads of different sizes were coated with different HIV proteins (p24, p31, gp41 and gp120) capable of binding any HIV-antibody present in the test specimen, the presence of HIV-antibody could then be detected by a second fluorescent-labeled antibody. This testing method proved more sensitive and more specific than currently licensed enzyme-linked immunosorbent assays (ELISA) and Western blot tests when 126 coded blood samples were tested. Recombinant testing procedures are in current use in most blood banking facilities and laboratories that are using HIV screening tests for diagnostic purposes.
Dr. Yolken developed a simple HIV test that can be used for detection of antibody to HIV-1 in the Third World, where sophisticated laboratories are not available. The test uses a nitrocellulose dipstick with lysed whole HIV-1 and antihuman-IgG-biotin complex solution. The dipstick results, which are based on naked eye evaluations of the degree of surface color intensity, are available in 90 minutes and are not dependent on instrumentation. There was good correlation between the results of standard screening tests and the visual color assessments for this test.
Several investigators supported by this program have developed tests that do not rely on antibody formation. These tests could, at least theoretically, eliminate problems with the "window period." One NHLBI-supported contractor utilized the polymerase chain reaction (PCR) test, which is capable of detecting one molecule of viral DNA in ten microliters of blood. Such a level of sensitivity, unparalleled by any other procedure, is derived from the ability of the enzyme reaction to replicate HIV-DNA to quantities that allow detection of the viral gene: over a billion copies of HIV-DNA in less than three hours. In an effort to adapt PCR technology for use in the clinical laboratory and blood bank settings, he developed an assay that combines the high sensitivity and specificity of testing methods that detect DNA and RNA with the technical conveniences of the currently used enzyme immunoassay systems. Although the test in its current form is still too complex for individuals in most blood banks to perform, it has nevertheless provided a valuable research tool for verifying infection. Work continues to simplify the procedure so that it can be used in less sophisticated laboratories.
Other uses for the PCR were investigated in this program. It was proven invaluable in evaluating the amount of virus in an infected individual's blood and in determining the rate at which HIV replicates. The PCR technique is currently used in clinical trials for monitoring the success of various forms of HIV therapy. Another investigator used the PCR to discriminate between true and apparent infections in babies born to infected mothers; such infants harbor maternal antibody and therefore routinely test HIV-positive with standard screening tests for the first 6 months of life, regardless of whether they are infected with HIV-1. PCR technology is also being used to monitor the effectiveness of drugs designed to prevent transmission of the virus from mother to fetus.
This contract program was designed to determine the effectiveness of efforts to eliminate HIV-1-infected units of whole blood, blood components (packed red cells, plasma, platelets, cryoprecipitate) or Factor VIII concentrates from the Nation's blood supply.
The program ended in 1992.
N01 HB67020 - Girish Vyas - University of California, San Francisco, CA
N01 HB67025 - Kenrad Nelson - Johns Hopkins University, Baltimore, MD
These NHLBI-supported investigators evaluated the frequency of HIV-1-infected seronegative blood. In a large cohort of patients who received transfusions during cardiac bypass surgery, only two HIV-1 sero-conversions occurred in patients without other identifiable risk factors, even though 110,000 units of blood were transfused. In another study investigating 61,000 units of blood that tested HIV-1-seronegative by ELISA, only one unit was found to be HIV-1-infected when confirmatory tests employing HIV-1 culture and the PCR (a sensitive technique for detecting viral DNA) were used. Donors were people with high-risk lifestyles. These investigators found that the risk of receiving a unit of blood that was HTLV-positive was 0.0039-0.0079 percent before screening of blood for HTLV was instituted in 1990 and 0-0.0015 percent after screening was instituted.
This contract program maintains a colony of chimpanzees that is available for research on post-transfusion viral hepatitis or AIDS. The repository, which initially was used only by the Transfusion Safety Study, currently stores clinical samples for the retrovirus epidemiology study (HB-90-01), which started in fiscal year 1989, and the study of pulmonary complications of AIDS (HR-87-09), which started in fiscal year 1987.
The program consists of one ongoing contract.
N01 HB77029 - William Goodwin - Southwest Foundation of Biomedical Res., San Antonio, TX
This contract program maintains collections of blood specimens for NHLBI-sponsored studies to make them available to the scientific community, particularly for research in transfusion medicine. Samples from the Retrovirus Epidemiology Blood Donor Study (HB-89-01), the Transfusion Safety Study (HL-83-15), and the study of the Pulmonary Complications of AIDS (HR-87-09) are stored in the repository.
One contract was awarded and support is ongoing.
N01 HB77027 - Susan Stern - ERC Bioservices Corporation, Rockville, MD