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 data5972 HIV-EIA RR donations at BSL, 04/99 - 07/03 Western Blot Result * 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
Correlation of Routine HCV NAT Screening with Supplemental HCV Serological Data12,385 HCV EIA RR Donations at BSL, 4/99 - 07/03 RIBA Result Total * 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
Effect of RNA Load & Storage on HIV Transmission 6 RBC (+) RBC (–) Platelets (+) FFP (+) FFP (–) 5 4 HIV-1 RNA Load (Log10) Copies/mL 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 recipientsOperskalski et al. submitted
Insert additonal breakout slides for HCV discordants, and several of leslie’s slides on ID retest.