Unexplained hepatitis C virus antibody seroconversion in established blood donors.
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BACKGROUND & AIMS: Impaired T-cell reactivity is believed to be the dominant cause of chronic hepatitis B virus (HBV) infection. We characterized HBV-specific T-cell responses in chronic hepatitis B surface antigen carriers who received bone marrow from HLA-identical donors with natural immunity to HBV and seroconverted to antibody to hepatitis B surface antigen. METHODS: T-cell reactivity to HBV antigens and peptides was assessed in a proliferation assay, the frequency of HBV core- and surface-specific T cells was quantified directly by ELISPOT assays, and T-cell subsets were analyzed by flow cytometry. RESULTS: CD4+ T-cell reactivity to HBV core was common in bone marrow donors and the corresponding recipients after hepatitis B surface antigen clearance, whereas none reacted to surface, pre-S1, or pre-S2 antigens. Furthermore, CD4+ T cells from donor/recipient pairs recognized similar epitopes on hepatitis B core antigen; using polymerase chain reaction for the Y chromosome, the recipients' CD4+ T lymphocytes were confirmed to be of donor origin. The frequency of core-specific CD4+ and CD8+ T cells was several-fold higher than those specific for surface antigen. CONCLUSIONS: This study provides the first evidence in humans that transfer of hepatitis B core antigen-reactive T cells is associated with resolution of chronic HBV infection. Therapeutic immunization with HBV core gene or protein deserves further investigation in patients with chronic hepatitis B.
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Post-exposure prophylaxis with antiretroviral drugs for at-risk needlestick injuries has become routine practice and is usually empirical. With increasing numbers of treatment-experienced patients, the choice of antiretroviral may need to be individually tailored. Infection can still occur despite attempts to optimize the drug combination used.
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Direct measurement of the incidence of infection with the human immunodeficiency virus (HIV)--the rate of new HIV infection--is vital if we are to understand better the dynamics of the current epidemic of HIV infection. Because soldiers are periodically and routinely screened for antibody to HIV, it is possible to measure the incidence of HIV infection directly in this large, demographically well-characterized population of young adults. To determine the incidence of HIV infection in this population, we examined test results reported by the U.S. Army's routine antibody-screening programs. During the first two years of the screening programs, the observed incidence of HIV infection was approximately 0.77 per 1000 persons per year. This rate was higher than expected on the basis of previously published estimates of seroprevalence in the Army (approximately 1.50 per 1000). On the basis of this annual incidence, and assuming it to be stable, we estimate that approximately 600 soldiers will become infected with HIV each year. The observed rate in the Army may be lower than the incidence of HIV infection in the corresponding demographic groups within the general U.S. population.
Patients with hemophilia A or von Willebrand's disease who are treated with concentrated preparations of human factor VIII made from unscreened pooled plasma are at substantial risk of contracting human immunodeficiency virus (HIV) infection. The purpose of this study was to investigate whether by treating such patients with a pasteurized factor VIII concentrate that had been heated in aqueous solution at 60 degrees C for 10 hours, HIV infection could be avoided. Eleven hemophilia centers in the Federal Republic of Germany and two in Austria identified 155 eligible patients who had been treated exclusively with pasteurized factor VIII concentrate and had not received any other blood products. Between February 1979 and December 1986 they received a total of 15,916,260 IU of pasteurized factor VIII. The United States was the source of 80 percent of the plasma from which the concentrate was made. By September 1988, these 155 patients had been screened for antibody to HIV type 1 (anti-HIV-1) with a total of 657 tests; all were negative. Sixty-seven patients were also tested once for antibody to HIV type 2 (anti-HIV-2); all these tests were negative as well. It appears that pasteurization effectively inactivates HIV, even in plasma that is likely to be highly contaminated with the virus.
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