1. Deferral of MSM: Policy Analysis by Andrew I. Dayton

2. “U” (Undetectable Strains) “E” (Blood Bank Error) “F” (Test Failure) “W” (Window Period) “P” (Prevalence) “I” (Incidence) Quantitation of Errors I: How many infectious units will “get through?” Infectious Units in Potential Donors Infectious Units in Blood Supply Contribution to Errors* = P x U = P x E = P x F = I x W/365 Total Errors =  P x (U + E + F ) + I x (WP/365)} x Population

3.  Errors =  P x (U + E + F ) + I x (WP/365) } x  Population Quantitation of Errors II: How many Additional infectious units will “get through?” Total Errors =  P x (U + E + F ) + I x (WP/365)} x Population

4. Quantitation of Errors III:  Population òFDA is considering changing donor suitability criteria to defer for MSM behavior only within the last 5 years prior to donation. òHow many new individuals will join the set of donors who are not deferred by the questionnaire and thus have their units enter into the blood bank for testing? òWe need to know the size of the MSM population that has abstained from MSM behavior for 5 years or more. òWe need to know the frequency at which MSM can be expected to donate.

5. Quantitation of Errors III:  Population òWe need to know the size of the MSM population that has abstained from MSM behavior for 5 years or more. ò1.4x10 6 MSM in U.S.A. with 5 years abstention (Lynda Doll, CDC) òWe need to know the frequency at which MSM can be expected to donate.

6. Quantitation of Errors IV:  Population We need to know the frequency at which MSM with deferrable risk will donate. òGiven an MSM (5 yr.) population size of 1.4x10 6 and assuming a donation rate equivalent to the general population, 5%, a change to a 5 year deferral policy would result in 5% x 1.4x10 6, or 70, 000 new MSM “presenting to donate.” òHowever, some of these will already have been donating. How many? ò0ò0.57% of men who present to donate have deferrable MSM history (REDS). ò{ò{ (0.57%) x (4.5x10 6 ) } / 4.7x10 6 = 0.55% òOòOf approximately 9x10 6 donors per year, about half, 4.5x10 6 are male. òTòThe MSM population with deferrable risk = 4.7x10 6 òThe donor frequency of MSM having deferrable risk therefore = ò(number showing up to donate) / (population size) =

7. Quantitation of Errors V:  Population We need to know the frequency at which MSM with deferrable risk will donate. òOf the 1.4x10 6 who are newly eligible to donate, 0.55% or ~7,700 will have already been donating. Therefore, of the 70,000 MSM who would be expected to newly present, 7,700 have already been donating. òThus, changing the deferral policy to a 5 yr. Deferral for MSM behavior would result in approximately 62,300 new MSM presenting to donate blood.

8. Quantitation of HIV in newly-donating population: Prevalence Issues I Prevalence Errors = P x (U + E + F ) x  Population HIV Prevalence in MSM varies from 6% to 36%, depending on the population sampled. Average US prevalence is approx. 8%. Given that about 75% of these already know their seropositive status and can be expected to self defer, the average effective prevalence is about 2%. Undetectable Strains are ignored for lack of evidence that they represent a predictable threat.. Blood Bank Errors involving release of HIV positive units have not been reported. Errors, where they have occurred, have been pipetting errors and have occurred at the rate of 0.5-1.3 x 10 -3. Primary test failure, F is essentially 0.

9. Quantitation of HIV in newly-donating population: Prevalence Issues I Prevalence Errors = P x (U + E + F ) x  Population 2% 0 1.3x10 -1 0 62,300 2x10 -2 x 1.3x10 -3 x 62,300 = 1.6 NAT provides a minimum 20 fold of redundancy. Therefore, NAT reduces the introduced prevalence errors to: 0.081

10. Quantitation of HIV in newly-donating population: Prevalence Issues II Even this low number of 0.081 unit per year would decrease as HIV tests eliminate the effective prevalence amongst repeat donors from this category. However, this estimate was made assuming errors only came from performing tests (e.g., pipetting errors). Double testing (e.g. EIA & NAT) confers no protection against release errors. Release errors are difficult to quantify.

11. Prevalence Issues III : Release Errors HCVAnti- HBV-core Donations (‘99-’00) Hospital1470,000 Blood Center 01630,000 From ARCNET (7/1/98-6/30/99): anti-HCV+ 5013 anti-HBV-core + 26,854 # donations 5.9e6 Inappropriate release, New York State (out of 700,000 donations) HCVAnti-HBV- core 0.013 3.5e-4 0.017 Reported Incidents Release Rate

12. Prevalence Issues III : Release Errors How many HIV-positive units could be inappropriately released by changing to a 5 year MSM deferral policy? Hospitals (8%) Blood Centers (92%) HIV+ (MSM x I) 100 1,146 Rate 0.013 3.5e-4 # released 1.3 0.4

13. Quantitation of HIV in newly-donating population: Incidence Issues I Average incidence in MSM = approx. 3x10 -2 /PY Although the typical window period = 11- 16 days, in needlestick accidents followed post-exposure, 5% (2/50) seroconvert after the first 6 months. If we assume that there is 95% conversion (or 5% failure to convert) every 6 months, there should be an exponential drop of the probability of of a seroconversion that we can calculate. convert in 6 months (%) fail to convert in 6 months (%) WP units introduced into U.S. blood banks, from 62,300 MSM (#) 95% 5% 3x10 -5 Units 80% 20% 0.11 Unit 75% 25% 0.42 Unit

14. Quantitation of HIV in newly-donating population: Incidence Issues I convert in 6 months (%) fail to convert in 6 months (%) WP units introduced into U.S. blood banks, from 62,300 MSM (#) 95% 5% 3x10 -5 Units 80% 20% 0.11 Unit 75% 25% 0.42 Unit These calculations took into account the possibility of donor confusion or poor memory by assuming that a 5 yr. query was entirely ineffective except for the behavior within the last 3 years (i.e. A 3 yr. Deferral policy).

15. Analysis of 1 year deferral. A 1 year deferral policy would result in approximately 112,000 new MSM donors, or about 1.8 times as many as a 5 year deferral policy. This would result in about 0.15 new sero-positive units “escaping interdiction” per year from errors in performing tests and possibly as many as 3 units from errors in unit release. Also, a 1 year deferral policy poses potential “window period problems.”

16. Analysis of 1 year deferral (continued) If there is only 95% seroconversion every 6 months post HIV exposure, then 0.25% will seroconvert after the first year. Incidence X risk of conversion X population = # infected units* 2% X 0.25% X 112,000 = 3.1 *No correction factor for the window period is used in this calculation, because it is assumed that any delayed seroconverters are infectious for the entire time between HIV infection and seroconversion.

17. Summary of HIV Thus, for HIV, changing to a 5 year deferral policy for MSM behavior would result in minimal numbers of infectious unit slipping through the blood screening system in the first year, and probably less in subsequent years. Inappropriate release, primarily due to non-automated blood handling systems, remains the biggest risk factor.

18. HCV The prevalence of HCV in Non-IVDU MSM (~4%) is only about twice that of the general population (1.8%). Given the high sensitivity of anti-HCV EIA and the redundancy of HCV NAT, deferral of MSM would be only marginally effective in preventing HCV transmission.

19. HBV: Prevalence Issues I As with HIV, essentially all of the infectees who are going to seroconvert will have done so well before 3 - 5 years. Therefore “incidence” issues are of minor concern. The real danger is chronically infected donors. The prevalence of HBsAg-positivity in MSM is ~1%. Therefore 623 new HBsAg-positive units would present. However, Anti-HBV-core provides redundancy.

20. HBV: Prevalence Issues II How many HBsAg-positive units could be inappropriately released by changing to a 5 year MSM deferral policy? Hospitals (8%) Blood Centers (92%) HBsAg+ (MSM x PI) 50 573 Rate 0.013 3.5e-4 # released 0.64 0.2 Therefore changing to a 5-year MSM deferral would introduce minimal risk of HBV morbidity from blood transmission.

21. Residual Risk Estimated risk of viral infections in the US per 10 million donations by sources of risk.* VirusWindow Period Viral Variants Chronic Seronegative Carriers Testing Error Total HIV 24< 0.6< 0.10.425 HCV 80< 10 - 2011 91 - 111 AgentWindow Period Viral Variants Chronic Antibody- Negative Carriers Test Error Total HIV 12 - 13< 0.600 13 - 14 HCV 16 - 32000 16 - 32 PRE- NAT POST- NAT *Busch

22. Estimated Incidence of HIV in MSM, San Francisco Percent per Year ____Year____ 19972000 All MSM 1.1 1.9 MSM/IDU 2.0 4.6 MSM, non-IDU 1.0 1.7

25. CONCLUSION We have quantitatively analyzed the risks to the blood supply of changing the deferral of MSM from “…since 1977…” to “.. Within the last five years …” This analysis has taken into account prevalence and incidence issues, test sensitivity and testing errors and release errors.. This analysis has not summarized projected improvements in blood banking from improved automation, but does demonstrate that inappropriate release remains a significant risk.

26. CONCLUSION  Introduction of a 5 year floating deferral for MSM behavior, even using conservative estimates, would result in minimal increased morbidity from the blood supply by HIV, HCV or HBV.

27. CONCLUSION There is scientific data to support relaxation of the current MSM deferral policy which defers male donors who have had sex with another male, even one time, since 1977. A 5 year MSM deferral policy for blood donation would harmonize with the 5 year deferral policy for tissue donation.

28. Questions for the Committee: 1.Does the BPAC recommend that Men who have Sex with other Men (MSM) be deferred from donating blood for a period of five years following MSM activity, rather than being deferred for any MSM behavior since 1977?

29. Acknowledgements ARC Alan Williams Sue Stramer Roger Dodd AABB(NBDRC) Marion Sullivan CDCLynda Doll Ian Williams NIH Harvey Alter NYS Dept. of Helath Jeanne Linden UCSF Mike Busch FDA Andrew Dayton Jay Epstein Robin Biswas Indira Hewlett Hira Nakhasi Martin Ruta Ed Tabor Paul Mied