# Presentation: 689381

## FDA Workshop on Behavior-Based Donor Deferrals in the NAT EraLister Hill Auditorium, NIHBethesda, MarylandMarch 8, 2006Summary of the WorkshopAndrew I. Dayton, M.D., Ph.D., CBER

## Behavioral Deferrals for HCT/Ps are often Less Stringent than for Blood: Rationale(Ruth Solomon)

- More reliable answers to the donor history questionnaire if questions pertain to the recent past (e.g., in the past 5 years vs. since 1977)
- when the donor himself is not being questioned, but instead, the next-of-kin
- Limited availability of certain cells/tissue
- Need for HLA-matched cells (e.g., hematopoietic progenitor cells)
- Size restriction for pediatric tissues (e.g., heart valves)
- Differences in risk of viral transmission due to more extensive processing of some types of tissues
- Removal of blood and viable cells by extensive washing, use of isopropanol, hydrogen peroxide, irradiation, and proprietary methods for viral clearance

## Cees van der Poel, Sanquin

- European Blood Alliance decided not to change the present policy of permanent deferral of potential donors who have a history of MSM.
- Reasons for this deferral – such as summarised in this report - should be publicly communicated, preferably in collaboration with MSM representative groups.
- Questionnaire 2005 (G. Follea, France) 15/15 countries have permanent deferral of donors with sexual behaviour which puts them at high risk of acquiring severe infectious diseases.** **
- Further studies could be envisioned to asses the safety (multiple infectious disease incidence) of “low-risk” cohorts in comparison with presently accepted (new) donors.

## Committee on Equal Rights

- 	The case of 4 MSM against 4 blood banks:
-  Equal Treatment Act forbids discrimination in offering goods or services.
- MSM is a manifestation of sexual orientation.
- Verdict:
- No direct discrimination. The purpose of selection is to prevent virus infections including HIV.
- Homosexual men are disproportionately affected by the selection.
- There is indirect discriminatory distinction, however objectively justified and not disproportional given the interest of the recipients of blood.

## Matthew McKenna, CDC

- 450K-500K MSM (lifetime) infected with HIV in the United States
- 250K-300K IDU (lifetime) infected with HIV in the United States
- ~3/4 are diagnosed in both groups
- Incidence in MSM ~2-3% per year in high risk, 1% per year in low risk (stable)
- Incidence in IDU ~0.5-1% per year (declining)
- Overall prevention outcomes impact risk to blood supply

## Estimates of Past HBV (anti-HBc) & HCV (anti-HCV) Infection in Selected US Populations, Ian Williams, CDC

**X**

**X**

**X**

**Prevalence (%)**

## Ian Williams, CDC

- Incidence of acute HBV and HCV infection has declined in the past two decades
- Primary risk factors remain unchanged
- Transfusion historically was an important risk factor for infection (especially for HCV infection), but currently is extremely rare
- When transmission has been observed, it has been due to “window period” donations and not testing errors

## EIA Sensitivity to HTLV-IIEd Murphy, UCSF

- Liu  _Transfusion_ 1999 (USA IDU)
- Camb Biotech EIA 			530/557 (95.1%)
- Abbott 7A92 EIA 			554/557 (99.5%)
- Roche PCR 				474/557 (85.1%)
- (but 47 (7.5%) PCR+ among 627 NEG on all EIA’s)
- Poiesz _Transfusion_ 2000 (IDU & S. Amer Indian)
- Vironostika HTLV-I and –II		144/204 (71%)
- Camb Biotech HTLV-I + rgp21	155/204 (76%)
- Abbott HTLV-I and –Iib		159/204 (78%)
- HTLV-II research PCR		200/204 (98%)

## HTLV Risk Groups – USAEd Murphy, UCSF

- HTLV-I (0.01% in Current US Blood Donors)
- Japanese American, Caribbean, Central African ethnicity: 0.1% to 1%
- CSW (7%), STD clinics (0.4%)
- HTLV-II (0.02% in Current US Blood Donors)
- IDU: 0.5% to 17.6%, by city
- Sex partner of IDU: ~0.5%
- Native American: 2% - 3%

## HTLV-I and –II Residual RiskEd Murphy, UCSF

- Has not been estimated since Schreiber NEJM 1996
- Probably still 1-2 per million units
- Cold storage and leukoreduction probably reduce risk but inferential data only

## Conclusions from the Uganda Transfusion Study, Sheila Dollard, CDC

**2.3% of HHV-8 seropositive blood units led to infection of the transfused patient**
**Criteria for HHV-8 seropositive and seroconverter were very stringent, therefore this estimate is low **

## Prevalence of HHV-8 DNA in HIV+ MSM (without KS), Sheila Dollard, CDC

**Atlanta Longitudinal Study followed 50 MSM for 2 years**
**Patients had average of 6 follow-up visits, 3-6 months apart**
**32% of patients had detectable HHV-8 DNA in blood for two or more visits**
**The average viral load was 1720 copies per ml (range 100-6800)**

## Seroprevalence of HHV-8 in US Populations(Sheila Dollard)

| Group | HHV-8 +  |
| --- | --- |
| US Blood donors (screened) | 2-4 % |
| General Population; hospital control patients, general clinic patients, pregnant women | 2-10 % |
| Injection drug users; heterosexual, HIV- | 6-11 % |
| Injection Drug users; heterosexual, HIV+ | 13-18 % |
| Men who have sex with men (MSM), HIV- | 12-16 % |
| MSM; HIV+ | 40-50 % |
| Patients with Kaposi’s sarcoma | > 95 % |

## Summary of Error Detection Rates from Investigation of Ab / MP-NAT Discordant Cases, Mike Busch 

|  | Serology Errors | MP-NAT Errors |
| --- | --- | --- |
| # discordant cases studied | 91 (NAT+/Ab-) | 566 (Ab+/NAT-) |
| # FN test errors  detected | 4 (HCV)
 | 1 (HCV) |
| # RNA+/Ab+ units screened | 14,242
 | 2,716 |
| FN error rate     | 0.028 %
(1 in 3,560)              | 0.037 %
( 1 in 2,716 )                 |

*If exclude 1**st** year in system 1, serol error rate = 0.0084%*

## Odds of Having a Reactive Screening Test Result(Mike Busch)

**†**** ****Odds ratio adjusted for donor status, test-seeking behavior.**
** ****p<0.001**

## Quarantine Release Errors Calculated from Biological Product Deviation Reports

- Sharon O’Callaghan & Andrew Dayton
- Rate of Quarantine Release Errors in Hospitals is ~18 Times That of Blood Centers

|  | Blood Centers | Hospitals |
| --- | --- | --- |
| Confirmed Positive | 0.5 / 10,000 |  |
| Repeat Reactive | 0.4 / 10,000 | 7 / 10,000 |

## Conclusions:

- Infectious Risk as % of Current Risk

-  Prevalence invariant w.r.t. abstinence
- Effective prevalence
- NY data suggests caution (HIV/MSM)
- IDU dangerous (HCV & HTLV)

| Behavior | Agent | E*
BPDR% | E*
NY Data% |
| --- | --- | --- | --- |
| MSM 5yr | HIV | 1.7 | 25 |
|  | HBV | <0.2 | <3 |
| MSM 1 yr | HIV | 2.5 | 40 |
|  | HBV | <0.4 | <6 |
| IDU 1 yr | HIV | 5 | 75 |
|  | HBV | <2.4 | 2.8-7 |
|  | HCV | 40 | 60 |
|  | HTLV | 2100 | 2200 |

## IV.  Number additional potentially infectious units enter supply – MSM >5yr and MSM >1yrComparison Results   EQR NY State – Linden data and                     EQR BPDR data   -  to current risk (Steve Anderson)

## Commentary, Roger Dodd

- EIDs do not appear to have any overall common characteristics with respect to class of organism, transmission route or pathogenesis. Consequently, they cannot be considered as a homogeneous group
- All transfusion transmitted infections must necessarily have a blood-borne phase.
- This does not however, assure transmissibility by sexual or low-volume non-parenteral routes.
- Consequently, risk behaviors associated with such transmission routes are not common to all TTIs

## Conclusions, Celso Bianco

- Additional measures, if implemented, must apply to all donors. Measures restricted to at risk donors would not resolve issues of discrimination.
- Rapid HIV tests [used for pretesting] are not compatible with the cGMP requirements for collection facilities licensed by FDA
- Pre-testing of first time donors would have a severe impact on blood availability

## Conclusions, Celso Bianco

- Substantial operational improvements in the past few years have reduced risk of inappropriate release of marker positive components
- Based on the parameters we used, change of deferral of criteria for MSM from indefinite to 1 year could increase the risk of HIV by 1:46 million or one case each 32.8 years [different model than FDA]

## Questionnaire Issues(Kristen Miller)

- Factors Impacting Response Accuracy
- Sensitive/stigmatizing behaviors
- Motivation
- Literacy
- Respondent burden
- Time frame / memory problems
- Donor knowledge & understanding of risk