Anti-HBc Testing and Donor Reentry Results of a Pilot Study

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Anti-HBc Testing and Donor ReentryResults of a
Pilot Study

• Susan L. Stramer, Ph.D.
• American Red Cross
• Blood Products Advisory Committee Meeting
• Nov 4, 2005 (update from Oct 21, 2004 meeting)
• In collaboration with
• National Genetics Institute and Abbott
  Laboratories

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Anti-HBc TestingBackground

• Historical/present RR rates range from 0.4-1.6
• False positivity high
• 25-87 reported
• dependent on specificity of test used
• No confirmatory/supplemental tests
• 1X anti-HBc RR may donate again impact of RR
  notification
• 2X anti-HBc RR deferred
• Historical number of deferred donors who lack
  other deferral codes
• gt 200,000 April 1991-Dec 2003
• gt 500,000 nationwide since Feb 1987

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Anti-HBc TestingBackground

• Can an algorithm be validated to reenter deferred
  donors who are falsely anti-HBc reactive?
• If so, what would be the yield of reentry?
• Unanimous support from BPAC (Oct 21, 2004) for
  validation of a reentry algorithm
• Test a follow up sample by
• Highly sensitive HBV DNA assay (lt10 copies/mL)
• Alternate anti-HBc assay having improved
  specificity
• (and HBsAg)
• Above tests must be negative

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Anti-HBc TestingProject Yield Based on Current
2X Reactive Algorithm

• 3.9 million donors (6.5 million donations) from
  2000 studied
• 0.64 anti-HBc overall repeat reactive rate
• 1.37 from FT/0.24 from RPT donors
• 75 1X anti-HBc reactive donors became 2X on next
  donation (plus another 13 over next 3 years)
• 88 FT and 38 RPT
• Anti-HBc reentry algorithms projected to have
  higher yields if a different test is
  introduced i.e., blood system converts to a
  different method

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Reactive Rates for Anti-HBc (Ortho)through July
2005
Percent
Mean RR by NTL (FY2006)
NTL Percent N NTL Percent N NTL Percent N
DET 0.28 289,547 CHA 0.42 227,840 PHL 0.41 241,89
5 STL 0.32 216,655 POR 0.57 166,533
Mean RR 0.39
Total N 1,142,470
Mean IR 0.54
99
97
98
96
00
02
05
01
03
04
Month (1995-2005)
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Anti-HBc Results from Hema-Quebec
---------Ortho---------------
--------Abbott PRISM---------
without reductant
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Anti-HBc RR Donation PCR Testing (NGI)Pilot Study

• 3000 anti-HBc RR unlinked donations selected in
  2001 for further testing by NAT (HBV PCR at NGI)
• Surplus NAT samples in PPTs (limit contamination)
• Criterion for inclusion was nonreactive by all
  other test methods
• No preselection of 1X versus 2X anti-HBc RRs
• 3000 chosen to allow a large enough sample size
  to include significant numbers of 2X RR donors
• 23.6 of ARC donors over a comparable time were
  2X anti-HBc RR
• Approx 708 of 3000 were 2X anti-HBc RR

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Anti-HBc RR Donation PCR Testing (NGI)Pilot Study

• Samples tested individually by HBV DNA
• UltraQual 8-rxn, 0.2-mL input
• Reactivity in any of 8 tests Positive
• Sensitivity 9 IU/mL
• Conversion 3.44 copies/IU 31 copies/mL
• 19/3000 (0.63) samples reactive
• 11 lt 100 copies/mL
• Average of 1.7 per 8 reactions reactive
• 8 with viral loads of 100-500 copies/mL 287.5
  mean
• Average of 4.75 per 8 reactions reactive

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HBV DNA in anti-HBc-only units
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Anti-HBc RR Donation PCR Testing (NGI)Pilot Study

• 3000 samples tested by Abbott PRISM anti-HBcore
  using licensed lots
• Study initiated following qualification of PPTs
  on the PRISM and availability of licensed lots
• Assumption is that 19 HBV DNA positives would be
  PRISM anti-HBc reactive
• Anti-HBc nonreactive/DNA negative samples would
  represent eligible donors for reentry
• Testing completed
• Anti-HBc reactives investigated for anti-HBc IgM
  anti-HBs as samples volume allows
• Study ongoing

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PRISM HBcore
Reactive Non-Reactive Total
Positive 19 0 19
Negative 2335 (79) 638 (21) 2973
Total 2354 638 2992
NGI HBV UltraQual 1000
Mean S/CO 0.14 (range 0.02-0.49) S/CO lt
1.00 Reactive 7 Samples PCR Negative PRISM
HBcore QNS
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PCR (NGI) PCR (NGI) PCR (NGI) PRISM HBcore (S/CO lt 1.00Reactive PRISM HBcore (S/CO lt 1.00Reactive PRISM HBcore (S/CO lt 1.00Reactive
Qual SuperQuant (copies/mL) Pos Rx (out of 8) S/CO 1 S/CO 2 S/CO 3
ARCHBV-SL093 Positive 200 8 0.10 0.09 0.09
ARCHBV-SL057 Positive 100 1 0.24 0.25 0.23
ARCHBV-DT628 Positive lt 100 1 0.07 0.07 0.06
ARCHBV-S2089 Positive 100 2 0.07 0.07 0.07
ARCHBV-D2017 Positive lt 100 2 0.07 0.07 0.07
ARCHBV-S2061 Positive 500 7 0.29 0.28 0.28
ARCHBV-SD783 Positive 500 1 0.03 0.03 0.03
ARCHBV-SL333 Positive lt 100 1 0.42 0.37 0.37
ARCHBV-DT312 Positive 200 6 0.13 0.11 0.11
ARCHBV-DT664 Positive lt 100 1 0.25 0.24 0.23
ARCHBV-DT178 Positive lt 100 1 0.10 E (QNS) E (QNS)
ARCHBV-SD687 Positive lt 100 2 0.14 0.14 0.13
ARCHBV-SL169 Positive 500 5 0.49 0.49 0.49
ARCHBV-SL297 Positive lt 100 1 0.02 0.02 0.03
ARCHBV-DT483 Positive lt 100 2 0.05 0.05 0.04
ARCHBV-DT142 Positive lt 100 2 0.04 0.04 0.04
ARCHBV-SL244 Positive lt 100 3 0.03 0.03 0.03
ARCHBV-DT588 Positive 200 8 0.08 0.08 0.08
ARCHBV-SD784 Positive lt 100 3 0.02 0.02 0.02
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Summary and Conclusions

• Preliminary data indicate feasibility of anti-HBc
  reentry algorithm
• All 19 HBV DNA-positive samples detected as
  reactive by Abbott PRISM anti-HBcore ChLIA
• All 19 strongly anti-HBc reactive
• Mean S/CO 0.14 (range 0.02-0.49)
• Yield of reentry dependent on prior assay
• 25 for Ortho gt Ortho (1Xgt2X)
• 21 for Ortho gt PRISM (pilot study)
• 40 for Ortho gt PRISM (Hema-Quebec)
• ?? for Corzyme (prior Abbott) gt PRISM

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Subsequent Studies

• Approx 5000 deferred donors (2X, with anti-HBc as
  only deferral criterion and HBV DNA negative)
  from Oct 04-Sept 05 invited to provide follow-up
  sample under NGIs HBV IND
• Testing HBV DNA (NGI 5 copy/mL sens), HBsAg,
  anti-HBc (Ortho PRISM pending), anti-HBs
• Study will convert to Roches IND using FDA
  proposed anti-HBc reentry algorithm
• Licensed PRISM anti-HBcore and HBsAg
  nonreactives tested by investigational Roche HBV
  DNA protocol
• 10 eligible donors have provided a follow up
  sample
• 66 past HBV infection leaves 44 for reentry
• Yield dependent on PRISM anti-HBcore reactivity,
  but due to low participation rate, maximum is 4.4

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(No Transcript)
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Reactive 2994 (79) Nonreactive 782
(21)
HBV DNA Positives
?
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N of 3776 of Rx
Reactive 2994 79.29
Repeat Reactives 2989 79.16
Initial Reactive Only (rpt QNS) 5 0.13 0.17

S/CO Min (1st retest) 0.99
S/CO Max 0.01
S/CO Mean 0.23

N of 3776 of NRx
Non-Reactive 782 20.71
Non-Reactive 771 19.42
Initial Reactive (rpt nonreactive) 11 0.29 1.41

S/CO Min 1.89
S/CO Max 1.01
S/CO Mean 1.47
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Anti-HBc RR Units Tested by HBV PCR (NGI)

• anti-HBc RR donations tested by HBV PCR (N
  31,914)
• HBV PCR Pos N 2,669 (8.4)
• 1,002 (38) HBsAg Confirmed Pos
• 1,667 (62 or 5.2 total) HBsAg NR