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Incorporation of NAT into supplemental testing of
HCV and HIV seroreactive donors
Michael P. Busch
representing
Blood Systems Research Institute
Blood Systems Laboratories
University of California, San Francisco
BPAC, Sept., 2003
Integration of NAT results into
serological testing algorithms
• NAT introduced to detect seronegative HCV and
HIV window-phase infections
• NAT data is useful for resolving true infection
status of seroreactive donors for counseling
– HCV RIBA positive donors
– donors with indeterminate or negative supplemental
results
• NAT results may obviate serological
supplemental assays in some cases
• NAT may facilitate donor reinstatement
1. Incorporate NAT results into donor
counseling to reinforce diagnoses based on
supplemental serology
• HCV RIBA+ & HCV NAT+ : Infected w/ HCV
• HIV WB+ & HIV NAT+ : Infected w/ HIV
• p24 Ag Neut+ & NAT+ : Infected w/ HIV
• HCV RIBA- or ind & NAT- : Not infected
• HIV WB- or ind & NAT- : Not infected
• p24 Ag Neut- & NAT- : Not infected
2. Flag cases with discrepant NAT vs
supplemental serology for further testing,
special counseling and follow-up
• RIBA+ but MP-NAT-
– Resolved infection > low level viremia > FP RIBA
• WB+ but MP-NAT-
– FP WB > low level viremia > HAART Rx > HIV vaccine
• p24 Ag neut+ but MP-NAT-
– FP neut
• RIBA/WB neg/ind, but NAT+
– true infection w/ evolving or incomplete SC or FP NAT
3. Use of HCV NAT results in lieu of RIBA
in HCV supplemental serology algorithm
• HCV EIA RR donors with pos HCV NAT
– notify as HCV infected without RIBA
• consistent with CDC guidelines, general practice
• EIA RR donors with neg HCV NAT
– perform RIBA for counseling and lookback
• RIBA+: notify as probable resolved infection;
consider performing ID HCV NAT
• RIBA-/ind: notify as not infected
4. Incorporate HIV NAT and alternate HIV
EIA into algorithm for notification of HIV
seroreactive donors
• Perform licensed alternate EIA on all HIV-EIA RR
donations.
• Combine alternate EIA and HIV RNA results to
determine need for WB and frame donor notification
message
– if NR on alternate EIA and neg index donation NAT, notify as
non-infected and eligible for reinstatement
– if R on alternate EIA &/or pos index donation NAT, perform
WB and notify based on combined WB/RNA status
Correlation of routine HIV NAT Screening
with Supplemental HIV Serological data
5972 HIV-EIA RR donations at BSL, 04/99 - 07/03
Western Blot Result
NAT
Result Pos Ind Neg
Pos 267 2** 0
(dHIV R) (93%) (0.1%)
Neg 18* 2216 3468
(mTMA NR)
Total 286 2218 3468
* All NAT pool NR. At least 9 are autologous donations; 6/9 samples are from 3
donors. 1 donor gave a f/u sample that tested HIV EIA R, WB Neg and NAT NR.
**1 w/ 1+ p24 band; 1 w/ +/- p24, p55, gp120 & 2+ gp160 bands
EIA s/c and WB band data for 18 BSL donor
samples that tested WB pos / NAT neg
NAT HIV EIA HIV S/CO HIV S/CO HIV S/CO GS_BLOT E18 E24 E31 GS40 E41 E51 E55 E65 E120 E160
NR R POS + + +/- + + + + + + +
NR R 2.246 1.874 1.781 POS - + - - - - - - - +
NR R POS ++ ++ ++ ++ ++ ++ ++ ++ ++ ++
NR R 7.813 6.281 5.905 POS +/- ++ ++ ++ ++ ++ ++ ++ ++ ++
NR R 8.031 6.678 7.331 POS ++ ++ ++ ++ ++ ++ ++ ++ ++ ++
NR R 7.592 7.197 6.945 POS ++ ++ ++ ++ ++ ++ ++ ++ ++ ++
NR R 7.577 7.278 7.281 POS +/- + ++ ++ ++ + ++ ++ + ++
NR R POS - ++ + ++ + + ++ ++ + ++
NR R 6.722 6.878 6.879 POS + ++ ++ ++ ++ ++ ++ ++ ++ ++
NR R 7.624 6.28 6.089 POS ++ ++ ++ ++ ++ + ++ ++ ++ ++
NR R 7.93 8.062 7.843 POS ++ ++ ++ ++ ++ + ++ + ++ ++
NR R 7.519 7.888 7.473 POS ++ ++ ++ ++ ++ ++ ++ ++ ++ ++
NR R 6.994 7.003 7.385 POS + ++ ++ ++ ++ + ++ ++ ++ ++
NR R 7.331 6.898 7.427 POS +/- ++ ++ ++ + ++ ++ + ++ ++
NR R 7.314 6.691 6.965 POS +/- ++ +/- ++ + +/- ++ ++ ++ ++
NR R 6.985 6.196 7.042 POS +/- ++ ++ ++ ++ +/- ++ ++ ++ ++
NR R 7.492 6.574 6.716 POS + ++ ++ ++ ++ + ++ + ++ ++
NR R 7.577 7.105 6.563 POS ++ ++ ++ ++ ++ ++ ++ ++ ++ ++
WB band data for 2 BSL donor samples that tested
NAT pos / WB ind
dHIV HIV EIA GS_BLOT E18 E24 E31 GS40 E41 E51 E55 E65 E120 E160
R R IND - + - - - - - - - -
R R IND - +/- - - - - +/- - +/- ++
Correlation of Routine HCV NAT Screening with
Supplemental HCV Serological Data
12,385 HCV EIA RR Donations at BSL, 4/99 - 07/03
NAT RIBA Result
Result Pos Ind Neg
Pos 5220 49* 6**
(dHCV R) (78%) (3%) (.16%)
Neg 1483 1868 3759
(NAT Multiplex)
Total 6703 1917 3765
* RIBA Patterns: 13 w/ mult. HCV + SOD bands, 14 w/ c33c only, 22 w/ c22 only
** 2 w/ +/- reactivity in c33c. 1 w/ +/- reactivity in 511and c33c. 1 w/ +/- reactivity in
511, c33c and NS5. 1 w/ +/- reactivity in 511, c33c and C22.
HCV RIBA band pattern for 6 BSL samples with
HCV EIA-RR, RIBA-ind, NAT-pos results
NAT dHCV dHIV HCV EIA RIBA3_INTC511_100_3 C33C_3 C22_3 NS5_3 CSOD_3
R R NR R NEG - +/- - - -
R R NR R NEG +/- +/- - - -
R R NR R NEG +/- +/- +/- - -
R R NR R NEG - +/- - - -
R R N R NEG - - - - -
R R R R NEG +/- +/- - +/- -
Effect of RNA Load & Storage on HIV Transmission
HIV-1 RNA Load (Log10) Copies/mL 6
RBC (+)
RBC (–)
5 Platelets (+)
FFP (+)
FFP (–)
4
3
2
1
0 10 30 50
Days to Administration
Busch et al. JID 1994
Relation of HCV RNA level in anti-HCV+ units
and transmission to recipients
Operskalski et al. submitted
Transmission to Recipient
Donor RNA Total Exposed Seroconversion
Status
PCR(-)/TMA(-) 12 1 (8%)
PCR(-)/TMA(+) 10 10 (100%)
102 - 103.9 21 20 (95%)
> 104 64 63 (98%)
• Insert additonal breakout slides for HCV
discordants, and several of leslie’s slides on ID
retest.
