R01 HL48367 - Michael Busch - Irwin Memorial Blood Center, San Francisco, CA
The investigator had access to the Transfusion Safety Study (TSS) repository of blood samples from 96 members of 38 linked donor/recipient clusters. The TSS has enrolled HIV-positive donors and their blood product recipients prior to 1985. It also includes sex partners of recipients. Based on these samples there are three aims to the study: (1) to obtain viral isolates and purify nucleic acids, (2) to amplify entire env from end-point dilutions of leukocyte- and serum-derived DNA sequence V3, V4, V5 by making a divergence tree and following sequence changes over time so changes in individuals may be compared to others in the same cluster, and (3) to correlate results of Aim 2 with clinical progression.
This grant was supported from 1992 to 1997.
The demonstration of dual infection by, and recombination between two donor HIV strains in a transfusion recipient represents the first unequivocal documentation of these phenomena. Also, this further establishes the significance of genomic recombination in evolution of HIV quasispecies diversity in vivo. With respect to factors influencing initial infection, data from recipients of seropositive blood components, exposed hemophiliacs, and exposed sexual partners indicate that viral burden in the source inoculum is the major determinant of infection, not differences in viral strain or host susceptibility.
R01 HL33091 - Irwin Sarason - University of Washington, Seattle, WA
The goal of the project was to determine the behavioral factors involved in blood donation, to investigate why donors with risk factors continue to donate blood, and to ascertain why low-risk donors refrain from donating blood.
This grant was supported from 1984 to 1996.
A large randomized study was conducted in high schools throughout the country. The project is achieving its goal of developing video tapes that are convenient and effective in recruiting populations that need to be included in the donor pool and the deferral of those that are at risk of infection with HIV.
R01 HL43421 - James Matthews - Baylor University, Dallas, TX
The project's objectives were to use ultraviolet radiation to render blood bank products free from envelope viruses, including cytomegalovirus and HIV-1, and to kill malarial organisms and trypanosome known to be transmitted via transfusion.
This grant was supported from 1989 to 1994.
The investigator developed a process of "preactivation" of photosensitive dyes as means of viral elimination in blood. Merocyanine UV-irradiated before incubation with contaminated red blood cells has shown significant antiviral activity with no discernable effect on RBCs in short-term studies.
R01 HL36715 - Pearl Toy - University of California, San Francisco, CA
The aims of the study were to determine why autologous donation is under-utilized and to test whether an education program would increase the pre-donation rate and the number of patients who benefit.
This grant was supported from 1987 to 1993.
R01 HL49028 - John Baust - Cryomedical Sciences, Rockville, MD
The investigator has developed and characterized a family of aqueous blood substitutes which will be tested in an in vivo dog model. These solutions have already been evaluated in an ex-vivo rat heart model.
This grant was supported form 1991 to 1993.
R01 HL36158 - Toby Simon - University of New Mexico, Albuquerque, NM
The primary aim of this study was to assess whether the healthy elderly between 63 and 70 years of age, who have a low incidence of HIV-1 infection, can donate blood 4 to 5 times per year with no risk to their health status.
This grant was supported from 1987 to 1992.
R29 HL52225 - Debra Newton-Nash - Blood Ctr Southeastern Milwaukee, Milwaukee, WI
This investigator studied the production of anti-bodies that inhibit Factor VIII procoagulant function, particularly with regard to regulation by Factor VIII-specific T cells. These inhibitors provide a substantial cause of morbidity for hemophiliacs and are responsible for their requirement for large amounts of blood products, including Factor IX, which continues to be responsible for transmission of viral infections. In addition, coagulation concentrates are responsible for, and may be related to, substantial changes in the immune system seen in HIV-positive and -negative hemophiliacs. These investigators studied Factor VIII-dependent T cell proliferation, cytokine production and expression of activation markers.
This grant was supported from 1994 to 1996.
R01 HL42257 - John Sullivan - University of Massachusetts, Boston, MA
The long-term objectives of this project were to understand the immunological and virological factors involved in the pathogenesis of HIV-1 infection. The information will be useful in developing an effective vaccine for prevention of HIV infection. The major hypothesis tested was that strong virus-specific CTL responses and neutralizing antibodies are associated with a delayed progression of HIV-1-induced immune attrition. These studies focused on a cohort of 164 patients with hemophilia, 73 percent of whom have been infected with HIV-1 since 1981-83. In this cohort, the investigators have identified HIV-1-infected non-progressors, slow progressors and rapid progressors. Immunological and virological studies will be carried out on fresh and repository samples of sequential plasma and peripheral blood mononuclear collected prospectively during the course of the project. Viral isolates were characterized for cytopathic Epstein Barr virus and the investigators will measure CD4 T helper cell function to evaluate non-HIV-directed defenses.
This grant was supported from 1988 to 1997.
Data from this study add support to the concept that virus-specific cellular immune responses protect against CD4 cell loss and limit viral replication in vivo. Studies of the long-term non-progressor (LTNP) infected with HIV in this cohort suggest that a combination of viral and host factors affect disease progression. Detailed phenotypic characterization of viral strains from individuals with divergent courses on infection suggest that there may be viral strains which cause infection without disease progression due to reduced cytopathogenicity rather than reduced replication capacity.