1. 21th VHPB meeting on “Prevention of viral hepatitis in Italy: lessons learnt and the way forward” Catania, 7-8 november 2002 RESIDUAL RISK OF TRANSFUSION- TRANSMITTED HBV, HCV AND HIV INFECTIONS IN ITALY IN ITALY A. Zanetti Institute of Virology, University of Milan (Italy)

2. BLOOD TRANSFUSION SAFETY: PREVENTION STRATEGIES Selection of periodic, volunteer, unremunerated donors Evaluation of medical and personal history Confidential unit exclusion Implementation of donors screening Viral inactivation Proper use of blood, blood components and derivates

3. Residual risk of transfusion-transmitted viral infections (TTIs) (1) lMostly related to the use of blood donated during the window period, in which an acutely infected donor may harbor infectious viral particles in the absence of symptoms and antigens/antibodies lThe probability of transmitting blood-borne viruses through transfusion of screened blood is related to the length of the pre-seroconversion window and to the incidence of HBV, HCV, HIV infections among donors

4. Residual risk of TTIs (2) The magnitude of residual risk may differ within countries depending on: The magnitude of residual risk may differ within countries depending on: l sensitivity of screening assays l levels of HBV, HCV and HIV endemicity

5. Residual risk of TTIs (3) lIn most industrialized countries, the rates of TTIs is so low to render impossible the measurement trhough specific studies. lMathematical models have been developed.

6. Residual risk of transfusion-transmitted HBV, HCV, HIV by screened blood in Italy Aim of the study: Aim of the study: lTo assess the risk of transmitting HBV, HCV and HIV by transfusion of screened blood; lTo estimate the additional reduction in risk that may be achieved through the implementation of direct viral detection assays.

7. Study population Site Site: Lombardy Period Period: January 1996 - December 2000 N. records examined from periodic volunteer, unpaid donors volunteer, unpaid donors: 2,411,800 Mean donors per year Mean donors per year: 223,500 Donation index Donation index: 2.1 Laboratory Laboratory: 3 rd generation EIA supplemental assays

8. lThe residual risk of HBV, HCV and HIV transmission through antibody-screened blood, was calculated by multiplying the adjusted incidence of seroconverting donors, expressed per 10 5 person/years of observation, by the mean lenght * of the window period before seroconversion, expressed as a year fraction. Measurement of HBV, HCV, HIV residual risk * * according to Busch.

9. Reduction of HBV, HCV, HIV Residual Risk by NAT The yeild in reduction of transfusion-transmitted HBV, HCV and HIV for the use of NAT in combination with the existing serologic assays, was calculated by multiplying the incidence rates of seroconversion x 100,000 person-years by the estimated reduction in the length of the window-periods achieved with NAT and expressed as the reduction in residual risk per unit.

10. Estimated residual risk of transmitting HBV, HCV, HIV by transfusion of screened blood in Italy (1996-2000) Velati et al, Transfusion 2002 R esidual risk Estimated donations +ve (95% CI) during the window phase (95% CI) during the window phase x 10 6 donations (95%CI) x 10 6 donations (95%CI) HCV HCV 1 : 126.528 7.9 (100.000-175.438) (5.7 – 10.0) HBV HBV 1 : 90.000 11.0 (66.666-128.205) (7.8 – 14.9) HIV HIV 1 : 434.782 2.3 (33.333-588.235) (1.7 – 3.0)

11. Estimated residual risks to the blood supply in Europe and in the USA 0 2 4 6 8 10 12 14 16 18 1 Couroucé (1996); 2 Schreiber (1996); 3 Allain (1997) 15.83 2 6.92 3 6.92 3 8.45 1 13.5 HBV 15.0 3 15.0 3 9.7 2 9.7 2 4.48 1 4.48 1 7.7 HCV 2.03 2 2.03 2 1.75 1 1.75 1 0.58 3 0.58 3 2.2 Lombardy HIV Cases per 10 6 donations

12. Declining time to detection of HBV, HCV, HIV markers during the window phase following infection Infection HCV RNA HCV Ag EIA 3.0 EIA 2.0 EIA 1.0 0 13 1470 80150 (days) Infection HIV RNA p24 Ag EIA 3.0 0 11 1622 (days) HCV HIV Infection HBV DNA EIA 3.0 0 41 56 HBV

13. Estimated reduction of the residual risk of Estimated reduction of the residual risk of transfusion-transmitted HBV, HCV and HIV by implementation of NAT Estimated window Reduction Estimated Residual phase (days) % risk x 10 6 donations (95% CI) EIA NAT HBV HBV 56 41 27 8.3 (5.7 – 10.9) HCV HCV 70 12 83 1.3 (0.9 – 1.6) HIV HIV 22 11 50 1.1 (0.8 – 1.5)

14. Conclusions (1) The risk of acquiring HBV, HCV or HIV through transfusion is extremely low. Nevertheless the safety of blood supply remains a major source of Public concern, requiring a continuous effort to reach zero risk. Advances in viral inactivation thecnologies and the introduction of NAT offer the potential to increase the safety of blood supply.

15. Conclusions (2) Assays for the detection of HIV p24 Ag and HCV cAg can represent alternative to NAT that are easy to perform, compatible with the current EIAs and possibly less expensive. In the case of HIV, NAT is clearly more sensitive than p24 assay. In the case of HCV, NAT and HCV cAg show comparable clinical sensitivity (mean difference 1-2 days, range 0-10 days).

16. Conclusions (3) The risk of transmitting HBV, HCV and HIV by transfusion of screened blood collected from periodic donors, properly selected through volunteerism and appropriate medical history, is currently very low and can be reduced with the introduction of direct viral detection assays. The need for such assays may vary among countries depending on HBV, HCV and HIV endemicity, on healthcare resources and on the foreseen expected benefits and costs. Ethical and legal issues may also play an important role in policy decision making.