This contract study was designed to characterize alterations in immune function in heavily transfused patients and to determine the relationship between these alterations to HIV infection and AIDS. In the Transfusion Safety Study (TSS), a serum repository was established of blood specimens from donations prior to universal screening for HIV. The recruitment of donors, blood recipients, and hemophilia patients created an unparalleled database that has provided most of what is currently known about transfusion-transmitted HIV-1 infection, e.g., transmissibility, infectivity, product safety, risk factor characterization, immune system function, and viral synergism.
One contract was awarded and is ongoing.
N01 HB97074 - James Mosley - University of Southern California, Los Angeles, CA
Recent Progress
Factors influencing the transmission of HTLV-I, HTLV-II and HIV-1 from donors retrospectively documented to have been infected at blood donation were examined. Overall, 27 percent of the recipients of cellular blood components from donors positive for anti-HTLV-I and -II became infected as determined by specific polymerase chain reaction assays. Neither virus was transmitted by acellular components or frozen/washed red cells. There was no probable instance of transmission by blood components stored for >10 days prior to administration. For blood components stored for ó10 days, HTLV-I and HTLV-II were transmitted at the same rate, and controlled for refrigerator-storage time, transmission by platelets was similar to that of red cell components. In comparison, 89 percent of the recipients of anti-HIV-1-positive blood were HIV-1-infected, regardless of component type. Decreased transmission of HIV-1 following refrigerator storage did not occur for cellular components until <26 days had elapsed.
The TSS showed that transfusion of HIV-1-positive blood resulted in infection of 90 percent of the recipients. It also demonstrated that progression to AIDS after transfusion was similar to that reported for homosexual men and hemophiliacs, and was independent of progression in the donor. Using 8,500 samples from areas high in risk for HIV (the TSS donor repository of 1984-85), these investigators were able to demonstrate that p24 antigen screening would have a negligible impact on blood donor screening. This was statistically comparable to a study of 500,000 current donors. The TSS was the first study to show HIV seroconversion (6 instances) in hemophiliacs receiving dry heat-treated Factor VIII from donors who screened negative for HIV. The TSS documented transmission of HTLV-I to recipients of HTLV-I/II-indeterminate blood products. The TSS was the first study to document HTLV-II transmission by transfusion. These advances in scientific knowledge, as well as others, continue to be published and presented to the scientific community.
Idiopathic CD4+ T-lymphocytopenia (ICL) is a newly described phenomenon that is characterized by AIDS-like infectious diseases, immunodeficiency in which CD4+ lymphocyte counts are less than 300, and consistently negative tests for the presence of human immunodeficiency virus (HIV). TSS investigators have recently started to analyze their extensive database for study subjects with ICL. The investigators found that low CD4+ counts are rare among anti-HIV-negative volunteer blood donors and are generally associated with transient illnesses. If any unknown virus progresses similarly to HIV, CD4+ count donor screening would be a poor surrogate for its detection.
In August 1985, the TSS began accessing persons who were at risk of HIV infection because of exposure to blood components and/or clotting factor derivatives from pooled plasma. Among 4,018 persons enrolled in TSS, there were 2,192 not infected with HIV-1/2 or HTLV-I/II who had lymphocyte subset evaluations on at least two different occasions. Overall, there were 32 HIV-1-negative persons who had two or more CD4+ counts that were less than 300, a prevalence of AIDS-defining illness by the 1987 CDC criteria, and in whom there had been no instances of persistent symptoms or findings consistent with symptomatic HIV infection. Of these 32 cases, 14 were classified as having no definite reason that could account for such low CD4+ values, a prevalence of 0.6 percent.