Impact of changing donor demographics on HIV transmission risk: A ten year analysis of individual donation NAT screening IPFA Lisbon 216 Marion Vermeulen
Disclaimer Race classifications are described as per the South African government classifications and are not meant to be discriminatory nor pejorative.
Background on HIV epidemic Antenatal Survey % 35 Blood donors %,35 3,26 29,5,3 25 22,8,23,25 2,22,2 15,15 1 5,6 1,74,5 RR 26/Million,1,5, Antenatal survey DoH blood donors SANBS
Collections by race and donor type 7 over 1 years 6 5 4 3 2 1 White Indian Coloured African New Rejoin Repeat
x/1 yields x/1 Concordants 12 1 HIV rate NAT yields serology yields Concordants 25 2 8 6 4 2 15 1 5 26 27 28 29 21 211 212 213 214 215
% Collections % HIV Collections and HIV rate in repeat donors 1% 9% 8% 7% 6% 5% 4% 3% 2% 1% % 26 27 28 29 21 211 212 213 214 215 African Non African African HIV+ Non African HIV +,3,25,2,15,1,5,
% Collection % HIV Collections and HIV rate in new donors 1% 9% 8% 7% 6% 5% 4% 3% 2% 1% % 26 27 28 29 21 211 212 213 214 215 African Non African African HIV+ Non African HIV + 3,5 3, 2,5 2, 1,5 1,,5,
x/1 x/1 HIV rates by donor type and classification 25 2 15 1 5 NAT yield rate 14 12 1 8 6 4 2 HIV concordants New Rejoin Repeat New Re-Join Repeat
Number (%) of HIV infection category New Rejoin Repeat Inter-don interval days (p)# Total NAT yields* 137 (1.3) 44 (1.9) 31 (12.) 11 (p<.5) 482 (3.1) Serology* Yields 186 (1.7) 17 (.7) 3 (.1) 781 (p<.5) 26 (1.3) Concordant 1545 (97.) 2285 (97.4) 228 (87.9) 231 1538 (95.6) Total 1868 (1) 2346 (1) 2512 (1) 15726 (1) *p value <.5 when comparing proportion of repeat and rejoin donors with new donors # p value <.5 when comparing interdonation intervals of NAT and serology yields with concordants (student t test)
Donor Type 25 2 15 1 5 Non African 4,5 4, 3,5 3, 2,5 2, 1,5 1,,5, Repeat Rejoin New Repeat Rejoin New Risk factors NAT yield/1 Ethnicity 35 3 25 2 15 1 African 7 6 5 4 3 2 1 5 White Indian Colour African Repeat Rejoin New
x/1 HIV NAT yield/1 by age and gender 5 45 4 35 3 25 2 15 1 5 16 to 19 2 to 25 26 to 3 31 to 4 41 to 5 51 to 6 16 to 19 2 to 25 26 to 3 31 to 4 41 to 5 51 to 6
% HIV by ethnicity and donor type Donor type Category Race New Rejoin Repeat p value (new vs repeat) HIV positives White.84.52.5 <.5 Indian.138.87.1 <.5 Coloured.573.354.47 <.5 African 2.335 1.143.214 <.5 Total 1.122.263.42 <.5 NAT yields White.5.9.7.98 Indian.25..16.9 Coloured.36.4.51.88 African.34.24.253.1 Total.142.5.5 <.5
p24 antigen reactivity (%) of NAT yields Negative Positive Total 26 8 (53) 7 (47) 15 27 11 (38) 18 (62) 29 28 24 (73) 9 (27) 33 29 26 (68) 12 (32) 38 21 28 (68) 13 (32) 41 211 39 (63) 23 (37) 62 212 3 (55) 25 (45) 55 213 5 (67) 25 (33) 75 214 37 (63) 22 (37) 59 215 32 (53) 24 (43) 56 Total 285 (62) 178 (38) 463
Early dynamics of HIV markers and estimates of lengths of WPs 1 7 1 4 2.7.1 3 rd gen Western blot 2 nd gen 4.3 14.4 19.7 22.9 25.7 Weusten J et al. Transfusion 211;51:23-15 Zaaijer et al. Lancet 1992;34:77-2 Fiebig EW et al. AIDS. 23;17: 1871-9. Apertrei AIDS 1996;1:F57-6 Vermeulen et al, Transfusion 213;53:2384-2398 days Source of data 4.3 1.1 Weusten 5.3 Vermeulen 1.1 6.3 3.2 Clade B seroconversion panel data 2.8 Fiebig Zaaijer 5. 38% p24ag+ Apetrei 3rd gen 2.7 3 rd gen Non clade B (A, E, G) seroconversion data Clade C NAT vs p24 Ag yield ratio data
Residual risk methodology Incidence rate-wp risk day equivalent model 1 No Repeat donations No. Seroconverting donors Harmonic mean of interdonation interval MID 5 = 1 95% LOD = 18.4 copies/ml* 5% LOD = 2.7 copies/ml* 2 copies/virion NAT WP 4.3 days NAT Yield WP ratio model 1,2 No of NAT yields No of donations NAT WP = 4.3 days NAT+ Ab- = 15.4 days (clade B) NAT+ Ab- = 16.4 days (clade C) NAT+,p24Ag- = 1.1 days NAT+, p24 Ag+=6.3 days RR = R Days N seroconverting repeat T between N repeat donations RR = WP NAT T1 (WP HIV Ab WP NAT)(T2) NNAT yields N all donations 1. Weusten Transfusion 211;51:23-15 2. Busch Transfusion 25;45:254-64
Comparison of models to determine residual risk per million WP Incidence rate-risk day equivalent model WP ratio model Lengths of WP used Repeat Lapsed Repeat + Lapsed Repeat + Lapsed Pre-NAT WP Clade B 14.58 13.77 14.52 14.15 Pre-NAT WP Clade C 14.58 13.77 14.52 13.29 Pre-p24 Ag WP Clade C 48.68 45.99 48.64 49.1 MID 5 =1 virion
Residual risk per million Number of HIV seroconversions Trend of residual HIV transmission risk 25 2 15 1 5 9 8 7 6 5 4 3 2 1 26 27 28 29 21 211 212 213 214 215 HIV seroconversion Risk days model WP ratio Model (MID 5 =1 virion, Clade C parameters)
Residual risk per million Trend residual HIV transmission risk by donor type 6 5 4 3 2 1 26 27 28 29 21 211 212 213 214 215 New Lapsed + Repeat All (WP ratio model, MID 5 =1 virion, Clade C parameters)
Residual risk per milion Trend residual HIV transmission risk by race 1 9 8 7 6 5 4 3 2 1 26 27 28 29 21 211 212 213 214 215 Non African African WP ratio model, MID 5 =1 virion, Clade C parameters)
Residual HIV transmission risk by donor type and ethnicity RR x:million (MID 5 =1) African Non African All New 79.7 3.1 38.1 Repeat & Lapsed 65.9 2.7 13.3 All 69.7 2.7 16.2 New 1:12,548 1:323,438 1:26,264 RR 1:x Repeat & Lapsed 1:15,174 1:37,342 1:75,47 All 1:14,349 1:371,776 1:61,557 WP ratio model, MID 5 =1 virion, Clade C parameters)
HIV ID-NAT breakthrough infection Donor Recipient Transfused unit Index donation Recipient Date Bled 19/9/214 4/12/214 14/2/215 Unit number 261167 26198447 Transfused date 28/9/214 Started ARV 28/1/215 Prism HIV S/CO.56 54.13 NAT S/CO.65 11.96 Viral load 936 copies/ml CD4 578 Lookback investigation HIV-1 Subtype C 1% boot strap in phylogenetic sequencing Observed risk 1:7.7 million
HIV NAT breakthrough cases Country Blood Product Storage Screening time Assay days 5% LOD cps/ml 95% LOD cps/ml Pool size Test Failure Break-Through Cases Approx Estimated Cps/mL Viral load plasma copies etimate method ml transfused Recipient Infected Reference Germany RBC In-house 96 64TaqMan 2 128, Yes Schmidt M et al. Transfusion 29;49:1836-1844 Germany RBC In-house 4.2 22.1 96 128TaqMan 2 256, Yes Chudy M et al. Transfusion.1537-2995.211.3281.x Viral Load Below Detectable Level Germany PLT In-house 24 TaqMan 24 No Kalus U et al., Transfusion 29;49:435-439 Germany RBC Gfe Blut 96 23.6 2 472 No Muller B. Transfusion. 213;53:2422-3 France RBC Nuclisens- Ampliscreen 1.9 15.5 24 45.65% LOD 2 912 Yes Najiouallah F et al. J Med Virol 24;73:347-349 USA FFP Duplex 2.1 15.6 16 33.65% LOD 2 672 Yes Phelps R et al. Transfusion 24;44:929-933 USA RBC Duplex 2.1 15.6 16 33.65% LOD 2 672 Yes Phelps R et al. Transfusion 24;44:929-933 USA FFP Duplex 2.1 15.6 16 33.65% LOD 2 672 Yes Stramer S et al. Transfusion 23;43:Supplement :4-41A USA RBC Duplex 2.1 15.6 16 33.65% LOD 2 672 No Stramer S et al. Transfusion 23;43:Supplement :4-41A USA RBC In-house 24 18NGI b 2 36 Yes Delwart ELet al. Vox Sang 24;86:171-177 Singapore PLT No NAT 5Probit 25 125 Yes Ling AE et al. JAMA 2; 28:4:21-214 Singapore RBC No NAT 5Probit 2 1 Yes Ling AE et al. JAMA 2; 28:4:21-214 S. Africa RBC No NAT 31Probit 2 62 No Ferriera MCet al. Transfusion 26;46:156-157 S. Africa PLT No NAT 31Probit 2 62 Yes Ferriera MCet al. Transfusion 26;46:156-157 Italy RBC No NAT 98TaqMan 2 196 No Zanetti et al. Transfusion 27;47:1328-1329 Denmark PLT In-house 96 246Abbott RT 25 615 Yes Harritshoj Let al. Transfusion 28;48:226-28 Denmark RBC In-house 96 246Abbott RT 25 492 Yes Harritshoj Let al. Transfusion 28;48:226-28 Japan RBC AmpliNAT 1.4 43.6 5 525% LOD 2 14 Yes Satake M et al. Journal of Hematology 24;8:36-1 USA RBC Duplex 2.1 15.6 16 33.65% LOD 2 672 Yes Laffoon et al, MMWR 21;59:1335-6 Greece RBC No NAT 2.1 15.6 4 8.45% LOD 2 168 Yes Hatzakis et al. (personal communication, 26) Spain RBC 28Ampliscreen 4.3 22.1 44 135 Ampl Monitor 2 27 No Alvarez et al. Transfusion 216;56;831 836 Spain PLT 2Ampliscreen 4.3 22.1 44 135 Ampl Monitor 65 8775 Yes Alvarez et al. Transfusion 216;56;831 836 Spain FFP-MB Ampliscreen 4.3 22.1 44 135Amp Mon 261 35235 Yes Alvarez et al. Transfusion 216;56;831 836 Japan RBC TaqScreen 4.1 28. 2 4.15% LOD 2 82 No Shinohar N. Transfusion 214;54:2361-2 Japan FFP TaqScreen 4.1 28. 2 4.15% LOD 24 984 Yes Shinohar N. Transfusion 214;54:2361-2 Brazil RBC 11in house 22.6 24 4.4probit 2 87 Yes Salles NA. Transfusion 213;53:2593-5 Thailand RBC TaqScreen 4.1 28. 6 24.6 5% LOD Rujirojindakul P. Vox Sang 215:19 Suppl 1 226 P-48 2 492 Yes (abstract) SANBS RBC Ultrio Plus 2.7 18.4 1 2.75% LOD 2 54 Yes Vermeulen M personal communication
probability HIV transmissibility in NAT breakthrough cases 1% 9% 8% 7% 6% 5% 4% 3% 2% 1% % FFP PLT RBC transmission MID 5 =96 copies= 48 virions Non transmission 1 1 1 1 1 1 copies/ml
Impact of MID 5 on overall residual HIV transmission risk MID 5 x/million 1:x 1 16 1:61,557 3.16 11.17 1:9,99 31.6 3.26 1:36,748 316.49 1:2,4,816 Observed rate.13 1:7,692,37 Possible reasons for lower observed rate: 5% mortality rate 18% adult population already infected Poor ability to contact patients post discharge
Conclusions Yield ratio and incidence rate models were comparable when using same WP (risk day) estimates No difference in residual risk between repeat and lapsed blood donors No difference in NAT yield rate and in residual risk in new, repeat or lapsed donors within African donors (and within non African donors) Difference and trends in NAT yield rate and residual risk depends on donor demographics Estimated residual risk is >1 fold than observed rate The implementation of ID-NAT has enabled SANBS to increase the African donor base and maintain the RR 18/million window period donations compared to 26/million in 25 (Pre-NAT)