Blood Products Advisory Committee 67th Meeting September 14, 2000

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Blood Products Advisory Committee67th Meeting
September 14, 2000

• Detection of HIV-1 p24 antigen positive donor
  specimens by Chiron TMA HIV-1/HCV assay
• Analytical sensitivity of Chiron TMA HIV-1/HCV
  assay on different HIV-1 subtypes

2
RSA Blood Donation

• Approximately one million units collected
  annually
• 57 by SABTS (Johannesburg), 18 by NBTS
  (Durban),
• 14 by WPBTS (Cape Town), 11 by four
  other Centers
• 90 from Low-Risk donors, 10 from
  High-Risk donors
• High HIV prevalence overall 0.21 (1997-1998)
• Repeat donors 8.7/10,000, first-time donors
  110/10,000
• Low-Risk donors 1.6/10,000, High-Risk
  donors 196/10,000
• Risk of transfusion-transmission estimated
  0.22/10,000 (1994)
• Donor selection and routine blood testing
• Voluntary with self-exclusion questionnaire,
  face-to-face interview
• HIV-1/2 Ab, HIV-1 p24, HCV Ab, HBsAg, syphilis
  serology
• Double EIA testing strategy

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RSA Study Study Design

• All seven Centers collecting voluntary blood
  donations participated
• 10,000 Low-Risk donors and 10,000 High-Risk
  donors
• Sample contribution proportional to collection
  volume
• Two EDTA plasma tubes shipped frozen to NAT
  laboratory at SABTS (Johannesburg) for individual
  TMA testing
• Routine serology results and donor demographic
  information collected prior to linkage breaking
  and TMA testing
• All positive samples shipped to BCP for
  additional testing

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RSA Study Donor Population

• Total Repeat First time
• number donors donors
• Low-Risk Male 6096 5465 631
• Female 3467 3038 429
• Total 9563 (46) 8503 1060
• High-Risk Male 6679 5720 959
• Female 4378 3334 1044
• Total 11057 (54) 9054 2003
• TOTAL Male 12775 (62) 11185 1590
• Female 7845 (38) 6372 1473
• Total 20620 (100) 17557 (85) 3063 (15)

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RSA Study Results

• TMA RR RR RR RR NR NR
• p24 Ag NR RR RR NR NR NR
• Antibody NR NR RR RR RR NR
• Low-Risk Male 0 0 0 2 0 6094
• Female 0 0 0 1 0 3466
• Total 0 0 0 3 0 9560
• High-Risk Male 0 1 5 58 0 6615
• Female 1 0 1 97 1 4278
• Total 1 1 6 155 1 10893
• TOTAL Male 0 1 5 60 0 12709
• Female 1 0 1 98 1 7744
• Total 1 1 6 158 1 20453

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RSA Study Preliminary Conclusions

• The number of HIV specimens identified in the
  RNA-window (1) and the p24-window (1) is lower
  than what was anticipated.
• The role of routine HIV p24 antigen testing
  should be re-evaluated.
• Automation and cost might be factors that will
  influence the decision on whether or not to do
  routine NAT testing.
• Nel TJ, et al. Abstract accepted by AABB 2000 for
  oral presentation

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Genomic Detection of HIV by TMA in High
Prevalence Areas of Sub-Saharan Africa

• Pool Pools Donors Pos. TMA p24 Ab
• size tested tested pools pos. pos.
  pos.
• S. Africa 24 126 3024 4 4 4
  b 0
• Ghana 11-25 140 2578 10 c
  8 a 0 6 b
• a Two TMA-positive / seronegative samples were
  confirmed by RT-PCR.
• b Included as positive controls.
• C Two contained HCV-pos samples, one with
  TMA-neg samples, one with QNSs.
• Allain JP, et al., abstract accepted by AABB 2000
  for oral presentation

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HIV-1 p24 Antigen Positive Donations a,b AIBC
(4/99 - 8/00)

• Sample Date TMA Multiplex
  TMA Disc HIV Serology
• ID Received Pool
  Single HIV-1 p24/Neut Ab/WB
• SF07989444 07/09/99 19.7
  19.0 18.8 R/P R/N
• SF08012675 08/27/99 17.1
  17.6 15.5 R/P R/P
• MM00124739 Sep 99 NT
  17.0 18.6 R/P R/N
• SF08051578 12/17/99 21.5
  22.4 21.7 R/P R/P
• SF08063998 02/01/00 19.6
  20.2 20.0 R/P R/P
• SF08107307 04/04/00 18.6
  21.1 20.1 R/P R/P
• a Total tested approximate 600,000 donations.
• b Data provided by Dr. Richard Gammon, South
  Florida Blood Banks.

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Detection of HIV-1 Type A Specimens by TMA Assay

• Subtype Copies/ml Origin
  Detection Source Testing Site
• A 29000 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• A 15000 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• A 7200 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• A 6000 Uganda 2/2 BBI WWRB302
  BBI/Chiron
• A 4600 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• A 2300 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• A 600 Ghana 2/2 BBI
  WWRB302 BBI/Chiron
• A 500 Ghana 2/2 BBI WWRB302
  BBI/Chiron
• A 200 Ivory Coast 2/2 BBI WWRB302
  BBI/Chiron
• A 600 Uganda 1/1 at 15 BBI WWRB301
  Chiron
• A 1000 Uganda 1/1 at 1100 BBI WWRB301
  Chiron
• A 1000 Ghana 1/1 at 1100 BBI WWRB301
  Chiron
• A 1000 Ghana 1/1 at 1100 BBI WWRB301
  Chiron
• A 600 Ghana 1/1 at 1100 BBI WWRB301
  Chiron
• A lt 400 Ghana 1/1 at 1100 BBI WWRB301
  Chiron
• A lt 50 Uganda 1/1 at 15 BBI WWRB301
  Chiron
• A lt 50 Ghana 1/1 at 1100 BBI WWRB301
  Chiron

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Detection of HIV-1 Type B Specimens by TMA Assay

• Subtype Copies/ml Origin Detection
  Source Testing Site
• B 30000 2/2 Necker ARN 99
  Lille, FR Montpllier, FR
• B 20000 USA 2/2 BBI WWRB302
  BBI/Chiron
• B 8200 2/2 Necker ARN
  99 Lille, FR Montpllier, FR
• B/D 5000 USA 2/2 BBI WWRB302
  BBI/Chiron
• B 3700 2/2 Necker ARN
  99 Lille, FR Montpllier, FR
• B 2000 China 2/2 BBI WWRB302
  BBI/Chiron
• B 1800 2/2 Necker ARN
  99 Lille, FR Montpllier, FR
• B 900 Argentina 2/2 BBI
  WWRB302 BBI/Chiron
• B 40000 Egypt 1/1 at 1100 BBI
  WWRB301 Chiron
• B 20000 China 1/1 at 1100 BBI
  WWRB301 Chiron
• B 20000 China 1/1 at 1100 BBI
  WWRB301 Chiron
• B 100 160/160 WHO
  Standard Gen-Probe
• B 100 5/5 VQA 003ru Lille,
  FR
• B 100 20/20 VQA
  Panel Hokkaido, JP

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Detection of HIV-1 Type B Specimens by TMA Assay

• Subtype Copies/ml Origin Detection Source
  Testing Site
• B 9000 RSA 1/1 at 1100 BBI WWRB301
  Chiron
• B 6000 China 1/1 at 1100 BBI WWRB301
  Chiron
• B 50 6/6 VQA 003ru Lille, FR
• B 50 19/20 VQA Panel Hokkaido, JP
• B 5000 China 1/1 at 1100 BBI WWRB301
  Chiron
• B 5000 USA 1/1 at 1100 BBI WWRB301
  Chiron
• B 4000 China 1/1 at 1100 BBI WWRB301
  Chiron
• B 30 155/160 WHO Standard Gen-Probe
• B 25 2/2 Pelicheck S2091 Lyon, FR
• B 20 20/20 JRC Standard Panel Hokkaido,
  JP
• B 10 20/20 JRC Standard Panel Hokkaido,
  JP
• B 8 2/2 Pelicheck S2091 Lyon, FR
• B 200 China 1/1 at 1100 BBI WWRB301
  Chiron

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Detection of HIV-1 Type C Specimens by TMA Assay

• Subtype Copies/ml Origin
  Detection Source Testing Site
• C 70000 Mozanbique 2/2 BBI
  WWRB302 BBI/Chiron
• C 20000 Uganda 2/2 BBI
  WWRB302 BBI/Chiron
• C 9300 2/2 Necker ARN 99
  Lille, FR Montpllier, FR
• C 80000 Zimbabwe 1/1 at 1100
  BBI WWRB301 Chiron
• C 700 Zimbabwe 2/2 BBI
  WWRB302 BBI/Chiron
• C 390 2/2 Necker ARN 99
  Lille, FR Montpllier, FR
• C 300 Zimbabwe 2/2 BBI
  WWRB302 BBI/Chiron
• C 30000 RSA 1/1 at 1100
  BBI WWRB301 Chiron
• C 30000 RSA 1/1 at 1100
  BBI WWRB301 Chiron
• C 30000 India 1/1 at 1100
  BBI WWRB301 Chiron
• C 700 RSA 1/1 at 15 BBI
  WWRB301 Chiron
• C 4000 Zimbabwe 1/1 at 1100
  BBI WWRB301 Chiron
• C 3000 India 1/1 at 1100
  BBI WWRB301 Chiron
• C 2000 Zimbabwe 1/1 at 1100
  BBI WWRB301 Chiron
• C lt 50 RSA 1/1 at 1100
  BBI WWRB301 Chiron
• C lt 50 Zimbabwe 1/1 at 1100
  BBI WWRB301 Chiron

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Detection of HIV-1 Type D Specimens by TMA Assay

• Subtype Copies/ml Origin
  Detection Source Testing Site
• D 50000 Uganda 2/2 BBI WWRB302
  BBI/Chiron
• D 10000 Uganda 2/2 BBI WWRB302
  BBI/Chiron
• D 4800 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• D 3000 Uganda 2/2 BBI WWRB302
  BBI/Chiron
• D 800 Uganda 2/2 BBI WWRB302
  BBI/Chiron
• D 490 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• D 7000 Uganda 1/1 at 1100 BBI
  WWRB301 Chiron
• D 3000 Uganda 1/1 at 1100 BBI
  WWRB301 Chiron
• D 1000 Uganda 1/1 at 1100 BBI
  WWRB301 Chiron
• D lt 50 Uganda 1/1 at 15 BBI
  WWRB301 Chiron

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Detection of HIV-1 Type E Specimens by TMA Assay

• Subtype Copies/ml Origin
  Detection Source Testing Site
• E 7700 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• E 3000 Thailand 2/2 BBI WWRB302
  BBI/Chiron
• E 1500 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• E 300 Thailand 2/2 BBI WWRB302
  BBI/Chiron
• E 100 20/20 VQA Panel Hokkaido, JP
• E 10000 Thailand 1/1 at 1100 BBI
  WWRB301 Chiron
• E 50 20/20 VQA Panel Hokkaido, JP
• E 20 19/20 VQA Panel Hokkaido, JP
• E lt 50 Thailand 2/2 BBI WWRB302
  BBI/Chiron
• E lt 50 Thailand 1/1 at 15 BBI
  WWRB301 Chiron
• E lt 50 Thailand 1/1 at 120 BBI
  WWRB301 Chiron

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Detection of HIV-1 Types F,G,H,O Specimens by TMA
Assay

• Subtype Copies/ml Origin
  Detection Source Testing Site
• F 48000 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• F 5900 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• F 200 Argentina 2/2 BBI WWRB302
  BBI/Chiron
• F 10000 Argentina 1/1 at 1100 BBI
  WWRB301 Chiron
• F 9000 Argentina 1/1 at 1100 BBI
  WWRB301 Chiron
• F lt 50 Argentina 1/1 at 15 BBI
  WWRB301 Chiron
• G 48000 2/2 Necker ARN 99 Lille,
  FR Montpllier, FR
• G 3100 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• G lt 50 Ghana 1/1 at 110 BBI
  WWRB301 Chiron
• G lt 50 Ghana 1/1 at 110 BBI
  WWRB301 Chiron
• H 9500 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• H 1400 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• O lt150 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• O lt150 2/2 Necker ARN 99 Lille, FR
  Montpllier, FR
• O lt 50 Spain 2/2 BBI WWRB302
  BBI/Chiron
• O lt 50 Cameroon 1/1 at 1100 BBI
  WWRB301 Chiron

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Detection of Specimensa with Different HIV-1
Genotypes by TMA Assay (Montpellier, France)

• Genotypeb Origin Detection Genotypeb
  Origin Detection
• A/E/- Cambodia 1/1 -/A/AG Cameroon 1/1
• A/E/- Cambodia 1/1 -/A/G Cameroon 1/1
• A/E/- Cambodia 1/1 -/A/G Cameroon 1/1
• A/E/- Cambodia 1/1 F1/F1/F1 Chad 1/1
• -/D/F3 Cameroon 1/1 -/A/G RCA 1/1
• -/A?/D Cameroon 1/1 C/C/- Djibouti 1/1
• -/D/D Cameroon 1/1 C/C/- Djibouti 1/1
• -/D/D Djibouti 1/1 -/O/O Cameroon 1/1
• F3/F3/F3 Cameroon 1/1 -/O/O
  Cameroon 1/1
• F2/F2/F2 Cameroon 1/1 -/B/-
  Montpellier 1/1
• F2/F2/F2 Cameroon 1/1 -/A/AG
  Cameroon 1/1
• -/G/G Cameroon 1/1 A/A/J Cameroon 1/1
• C/C/- Djibouti 1/1 A/A/- Djibouti 1/1
• C/C/- Djibouti 1/1 A/A/- Djibouti 1/1
• -/A/AG Cameroon 1/1 A/A/- RCA 1/1
• a ETSLR Panel, viral loads unknown b gag/pol/env

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CONCLUSIONS

• Of the three studies, all 17 HIV-1 p24 antigen
  positive specimens were also positive in Chiron
  TMA HIV-1/HCV assay
• Chiron TMA HIV-1/HCV assay has a ? 95
  detectability at 100 copies/ml for all HIV-1
  subtypes