Inactivation of viruses found with plasma proteins.

Plasma protein solutions such as albumin and intramuscular immune globulin have long histories of viral safety. Coagulation factor concentrates as traditionally manufactured frequently transmitted HBV, HCV, and HIV. Indeed, it is probable that every vial of concentrate contained infectious HCV. Modern coagulation factor concentrates have a greatly improved safety record arising, principally, from the implementation of virucidal procedures. It is interesting to note that the same methods that failed to substantially reduce NANBHV transmission in clinical studies are those that were found to inactivate less than 10(4) ID50 of HIV, HBV, and/or HCV in preclinical studies (Table 17-5). Implementation even of these methods nearly eliminated the transmission of HIV by coagulation factor concentrates. A summary of the results of the most successful procedures is given in Table 17-10. The results show 0/564 patients had evidence of HIV transmission, 6/151 patients had evidence of HBV transmission, and 2/301 patients had evidence of HCV transmission. As compared with those procedures described in Table 17-5, the greater kill of HIV, HBV, and NANBHV demonstrated preclinically, and the improved clinical results, are most notable. The data, examined in terms of units transfused, are presented in Figure 17-1. Since the average adult hemophiliac in the United States receives 80,000 units of clotting factor per year, the best of the concentrates show safety over the equivalent of at least 10-human-years of treatment. Are the best of today's coagulation factor concentrates safe from the transmission of HBV, NANBHV (including HCV), and HIV. Given the limited number of patients eligible for clinical studies, and the length, difficulty, and expense of such studies, the best answer comes from a knowledge of the initial virus load coupled with information regarding virus removal, serendipitous inactivation, and intentional sterilization. A recently completed analysis of these factors (Horowitz 1990) indicates that the best of the modern coagulation factor concentrates are likely to be as safe as albumin (Figure 17-2).