Sterilisation of hepatitis and HTLV-III viruses by exposure to tri(n-butyl)phosphate and sodium cholate.

Blood product sterilization with 0.3% tri(n-butyl)phosphate (TNBP)/0.2% sodium cholate (CA), a combination known to permit high recovery of factor VIII and factor IX, was evaluated for its effect on hepatitis B (HBV), non-A, non-B (NANB), and human T-lymphotropic type III (HTLV-III) viruses. 2 chimpanzees received factor VIII preparations contaminated with 100,000 chimpanzee infectious doses of HBV and treated with TNBP/CA. Neither had evidence of HBV during the 9 month follow-up, but hepatitis B surface antigen (HBsAG) developed 5 and 6 weeks, respectively, after challenge with untreated inoculum. 2 chimpanzees were similarly exposed to NAMB inoculum treated with TNBP/CA. Neither became infected during 26 weeks of follow-up, but both had characteristic NANB-associated ultrastructural changes 3-5 weeks after exposure to untreated inoculum. 2 chimpanzees inoculated with TNBP/CA-treated factor VIII derived from a pool of 13 lots obtained from 5 US manufacturers remained free of any evidence of NANB infection during 32 weeks of follow-up. Subsequently, NANB infection developed in both animals 3-4 weeks after exposure to untreated inoculum. Exposure of HTLV-III diluted into a factor VIII preparation to TNBP/CA inactivated tissue culture infected doses within 20 minutes. These results demonstrate that exposure of labile blood derivatives to TNBP/CA effectively inactivates HBV, NANB, and HTLV-III viruses, although additional experiments with more potent inocula are needed to establish limits of inactivation efficacy against these agents. To provide absolute safety, a process efficacy of = or 5-6 log 10 is preferable.