# Presentation: 433633

## Blood Products Advisory Committee67th 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 **

## RSA Blood Donation

**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

## RSA Study: Study Design

**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

## RSA Study: Donor Population

**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%)**

## RSA Study: Results

**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**

## RSA Study: Preliminary Conclusions

**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** **

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

**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

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

**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.

## Detection of HIV-1 Type A Specimens by TMA Assay

**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 1:5****	****BBI WWRB301 ****	****Chiron****	**
**A****	****	****1000****	****  Uganda****	****        1/1 at 1:100****	****BBI WWRB301 ****	****Chiron****	**
**A****	****	****1000****	****  Ghana****	****        1/1 at 1:100****	****BBI WWRB301 ****	****Chiron****	**
**A****	****	****1000****	****  Ghana****	****        1/1 at 1:100****	****BBI WWRB301 ****	****Chiron****	**
**A****	****	****600****	****  Ghana****	****        1/1 at 1:100****	****BBI WWRB301 ****	****Chiron****	**
**A****	****	****< 400****	****  Ghana****	****        1/1 at 1:100****	****BBI WWRB301 ****	****Chiron****	**
**A****	****	****< 50****	****  Uganda****	****        1/1 at 1:5****	****BBI WWRB301 ****	****Chiron****	**
**A****	****	****< 50****	****  Ghana****	****        1/1 at 1:100****	****BBI WWRB301 ****	****Chiron****	**

## Detection of HIV-1 Type B Specimens by TMA Assay

**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 1:100        BBI WWRB301 ****	****Chiron****	**
**B****	****	****20000****	****  China****	****    1/1 at 1:100        BBI WWRB301 ****	****Chiron****	**
**B****	****	****20000****	****  China****	****    1/1 at 1:100        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****	**

## Detection of HIV-1 Type B Specimens by TMA Assay

**Detection of HIV-1 Type B Specimens by TMA Assay**

**Subtype****	****Copies/ml****	****  Origin****	****  Detection****	****	****Source****	****    ****	****     Testing Site****	**
**B****	****	****9000****	****  RSA****	****  1/1 at 1:100****	****BBI WWRB301 ****	****     Chiron****	**
**B****	****	****6000****	****  China****	****  1/1 at 1:100****	****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 1:100****	****BBI WWRB301 ****	****     Chiron****	**
**B****	****	****5000****	****  USA****	****  1/1 at 1:100****	****BBI WWRB301 ****	****     Chiron****	**
**B****	****	****4000****	****  China****	****  1/1 at 1:100****	****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 1:100****	****BBI WWRB301 ****	****     Chiron****	**

## Detection of HIV-1 Type C Specimens by TMA Assay

**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 1:100  ****	****       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 1:100****	****       BBI WWRB301    ****	****      Chiron****	**
**C****	****	****30000****	****  RSA****	****              1/1 at 1:100****	****       BBI WWRB301****	****      Chiron****	**
**C****	****	****30000****	****  India****	****              1/1 at 1:100  ****	****       BBI WWRB301****	****      Chiron****	**
**C****	****	****700****	****  RSA****	****              1/1 at 1:5****	****       BBI WWRB301****	****      Chiron****	**
**C****	****	****4000****	****  Zimbabwe             1/1 at 1:100  ****	****       BBI WWRB301****	****      Chiron****	**
**C****	****	****3000****	****  India****	****              1/1 at 1:100  ****	****       BBI WWRB301****	****      Chiron****	**
**C****	****	****2000****	****  Zimbabwe             1/1 at 1:100   ****	****       BBI WWRB301****	****      Chiron****	**
**C****	****	****< 50****	****  RSA****	****              1/1 at 1:100   ****	****       BBI WWRB301****	****      Chiron****	**
**C****	****	****< 50****	****  Zimbabwe             1/1 at 1:100  ****	****       BBI WWRB301****	****      Chiron****	**

## Detection of HIV-1 Type D Specimens by TMA Assay

**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 1:100****	****BBI WWRB301 ****	****Chiron****	**
**D****	****	****3000****	****     Uganda****	****         1/1 at 1:100****	****BBI WWRB301 ****	****Chiron****	**
**D****	****	****1000****	****     Uganda****	****         1/1 at 1:100****	****BBI WWRB301 ****	****Chiron****	**
**D****	****	****< 50****	****     Uganda****	****         1/1 at 1:5****	****BBI WWRB301 ****	****Chiron****	**

## Detection of HIV-1 Type E Specimens by TMA Assay

**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 1:100****	****BBI WWRB301 ****	****Chiron****	**
**E****	****	****50****	****	****          20/20****	****VQA Panel****	****	****Hokkaido, JP****	**
**E****	****	****20****	****	****          19/20****	****VQA Panel****	****	****Hokkaido, JP****	**
**E****	****	****< 50****	****       Thailand       2/2****	****	****BBI WWRB302 ****	****BBI/Chiron****	**
**E****	****	****< 50****	****       Thailand       1/1 at 1:5****	****BBI WWRB301 ****	****Chiron****	**
**E****	****	****< 50****	****       Thailand       1/1 at 1:20****	****BBI WWRB301****	****Chiron****	**
**	**

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

**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 1:100****	****BBI WWRB301 ****	****Chiron****	**
**F****	****	****9000****	****       Argentina    1/1 at 1:100****	****BBI WWRB301****	****Chiron****	**
**F****	****	****< 50****	****       Argentina    1/1 at 1:5****	****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****	****	****< 50****	****       Ghana****	****         1/1 at 1:10****	****BBI WWRB301 ****	****Chiron****	**
**G****	****	****< 50****	****       Ghana****	****         1/1 at 1:10****	****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****	****	****<150****	****	****         2/2****	****	****Necker ARN 99****	****Lille, FR; Montpllier, FR**
**O****	****	****<150****	****	****         2/2****	****	****Necker ARN 99****	****Lille, FR; Montpllier, FR**
**O****	****	****< 50****	****       Spain****	****         2/2****	****	****BBI WWRB302 ****	****BBI/Chiron****	**
**O****	****	****< 50****	****       Cameroon   1/1 at 1:100****	****BBI WWRB301 ****	****Chiron****	**

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

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

**Genotype****b ****   Origin****	****	****Detection****	****	****Genotype****b ****    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****	**

## 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**