AIDS, Blood Transfusions, and Directed Donations
Authors: T F Zuck, M S Preston, D L Tankersley, M A Wells, A E Wittek, J E Epstein, S Daniel, M Phelan, G V Quinnan
Journal: New England Journal of Medicine (1986)

Prince et al. (Feb. 6 issue) recently expressed concern that human T-cell lymphotropic virus Type III (HTLV-III) could be transmitted by intravenous immune globulin preparations.  They suggested that conditions used to make intermediate Cohn-Oncley fractions did not inactivate spiked HTLV-III; however they did not study partitioning of HTLV-III into the various fractions.  We recently reported the results of such studies.  HTLV-III was spiked into the various Cohn-Oncley fractions and its partitioning between precipitates and supernatants as well as inactivation was studied by viral cultures and quantitative antigen measurements by antigen-capture enzyme-linked immunosorbent assay (ELISA).  These studies showed that HTLV-III was partioned and inactivated at multiple steps in the Cohn-Oncley process.  At the most efficient step HTLV-III was quantitatively (99.5%) partitioned into precipitate III a fraction discarded during the manufacturer of immune globulin.  The cumulative effects of partitioning and inactivation resulted in a potential efficiency of virus removal of 10(15) infectious units per milliliter.  This efficiency is many orders of magnitude greater than would be needed to eliminate the small amounts of virus that potentially could be present in plasma pools used for immune globulin manufacture.  Thus the conjecture of Prince et al. that lyophilization of immune globulin would preserve HTLV-III infectivity is not relevant.  In addition not all intravenous preparations are lyophilized as they implied.  Surveillance studies of recipients of intravenous immune globulin suggested by Prince et al. have been under way since the autumn of 1985.  The number of patients is limited because most recipients are immunodeficient and would not be expected to acquire antibodies even if they were infected with HTLV-III.  Furthermore because immune globulin preparations may contain antibodies to HTLV-III patients receiving immune globulin on a long-term basis are unsuitable for study; antibody detected in serum samples from such patients could have been transferred passively.  Despite these limitations 134 recipients (mostly patients with immune thrombocytopenia but a few with renal transplants or Kawasakis disease) of intravenous immune globulin made by various manufacturers (data provided by J. Bussel M.D. The New York Hospital-Cornell Medical Center The Massachusetts Public Health Biologic Laboratories Miles Laboratories Travenol Laboratories The Blood Transfusion Service of The Swiss Red Cross Immuno AG and Kabi Vitrum AB) have been followed for 2 to 24 months by means of ELISA and Western blotting of serum reactive by ELISA.  3 patients had passively transferred antibodies; none produced HTLV-III antibodies.  Thus the results of laboratory studies of the fractionation process and surveillance of immune globulin recipients corroborate epidemiologic observations indicating that receipt of immune globulin is not associated with the risk of the development of AIDS.  (full text)