This work presents the current Pharmacovigilance systems and activities in Australia and New Zealand in Asia-pacific region

1. The ARCHITECT HIV
Ag/Ab Combo Assay
By Payam Javanmardi
Academy of Applied Pharmaceutical Sciences
Canada, Toronto, December 2014
1

2. On June 21, 2010 FDA approved the first Diagnostic
assay to detect both HIV Ag and Abs to Human
Immunodeficiency Virus.
This assay approved for use as an aid in the
diagnosis of HIV-1/HIV-2 infection in adults
including pregnant women.
It is also the first assay for use as an aid in the
diagnosis of HIV-1/HIV-2 infection in children as
young as two years old.
2

3. The ARCHITECT HIV Ag/Ab combo assay is not
intended to be used for routine screening of blood
donors.
It is approved as a donor screening assay for HIV-1/HIV-
2 infection in urgent situations where licensed blood
donor screening tests are unavailable or their use is
impractical.
3

4. Based on the Risk-based system of Health Canada,
ARCHITECT HIV Ag/Ab Combo Assays as a Donor
Screening IVDD is classified as Class IV with highest
risk potential.
Rule 1: An IVDD that is intended to be used to detect the
presence of, or exposure to, a transmissible agent in blood,
blood components, blood derivatives, tissues or organs assess
their suitability for transfusion or transplantation is classified
as Class IV
4

5. FDA approval is based on a clinical trial which
evaluated the assay in terms of Specificity,
Sensitivity, and Reactivity.
5

6. The sensitivity of a clinical test refers to the
ability of the test to correctly identify those
patients with the disease.
Sensitivity= TP/ TP+FN
6

7. The Specificity of a clinical test refers to the
ability of the test to correctly identify those
patients without the disease.
Specificity= TN/ TN+FP
7

8. The ARCHITECT HIV Ag/Ab combo assay is a
Chemiluminescent Microparticle Immunoassay (CMIA)
for the simultaneous qualitative detection of HIV gp24
Ag and Antibodies to HIV-1/HIV-2 in Human serum or
plasma
8

9. An Immunoassay technique in which the microparticle
bound antigen or antibody is labeled with a molecule
capable of emitting light during a chemical reaction.
This light is used to measure the formation of the Ag-Ab
complex.
9
What is CMIA?

10. The ARCHITECT HIV Ag/Ab Assay
Sample + Assay diluent + Paramagnetic particles
HIV p24 Ag and HIV-1/HIV-2 Abs present in the sample bind to the HIV-
1/HIV-2 Ags and HIV p24 Mab coated microparticles
*Washing
The acridinium –labeled Conjugate
Bound HIV p24 Ag and HIV-1/HIV-2 Abs bind to the conjugate of acridinium-
labeled HIV-1 Ags (recombinant), acridinium-labeled HIV-1/HIV-2 synthetic
peptides, and acridinium-labeled HIV p24 antibody.
*Washing
Pre-trigger (Hydrogen Peroxide) and Trigger (Sodium Hydroxide) Solutions
are added and chemiluminescence measured (RLU)
10

11. 11
Specimens that are initially reactive in the assay
should be retested in duplicate.
Repeat reactivity is highly predictive of the
presence of HIV p24 Ag and HIV-1/HIV-2 Abs.
However, as with all immunoassays, the
ARCHITECT combo assay may yield nonspecific
reactions due to other causes.

12. A repeatedly reactive specimen should be
investigated and confirmed further with sensitive,
supplemental HIV-specific tests, such as
immunoblots, antigen test, and HIV nucleic acid
test.
12

13. Evaluation of Diagnostic HIV Ag/Ab Combo Assay
ClinicalTrials.gov Identifier: NCT00933933
Study Type: Interventional
Study Design: Non-Randomized, Open Label, Single group
Assignment
Start Date: June 2009
Study Completion Date: November 2009
Study Phase: Phase 3
Sponsor: Abbott Diagnostics Division
Purpose: To test blood specimens using a new investigational
test that detects antigen and antibody to HIV. Results will be
compared to an approved HIV antibody test and supplemental
testing performed to determine HIV status. 13

14. Evaluation of Diagnostic HIV Ag/Ab Combo Assay
Primary Outcome Measures:
 ARCHITECT HIV Combo Test Data Clinical Specificity in
Population at Low Risk for HIV Infection
 ARCHITECT HIV Combo Test Data Clinical Sensitivity in HIV
Positive Specimens
 ARCHITECT HIV Combo Test Data for Specificity and
Sensitivity in Pregnant Female Population
 ARCHITECT HIV Combo Test Data for Specificity and
Sensitivity in Pediatric Population
14

15. Evaluation of Diagnostic HIV Ag/Ab Combo Assay
Secondary Outcome Measure:
 ARCHITECT HIV Combo Test Data for Reactivity of
ARCHITECT HIV Combo in increased HIV High Risk
Populations
Recruitment Details:
 All specimens collected under separate collection Protocols or
obtained from specimens Supplier;
 HIV Ag +/ HIV-1 Ab+ samples collected from Individuals at
Risk for HIV Infection in the USA
 HIV-2 Ab+ samples collected from HIV-2 endemic area(Ivory
Coast)
15

16. Evaluation of Diagnostic HIV Ag/Ab Combo Assay
Reporting Populations:
1. Specificity Population
 6146 Sp. from Apparently Healthy Individuals at Low Risk for HIV Infection (16-89Y)
Including 250 Sp. from Pregnant Females in First Trimester of Pregnancy
448 Sp. from Presumed HIV Negative Pregnant Females (16-44Y)
558 Sp. from Pediatric Presumed HIV Negative (2-16Y)
2. Sensitivity Population
 1287 Sp./Commercial Panel Members HIV-1 p24 Ag+, Sp. confirmed HIV-1 Ab+ and Sp.
confirmed HIV-2 Ab+
67 Sp. from Pregnant Females from all three trimester confirmed HIV Positive by
Supplemental Testing
3. Reactivity Population
 1206 Sp. from Individuals at increased Risk for HIV Infection (16-89Y) from US and HIV-2
Endemic area
203 Sp. from Pregnant Females at Risk for HIV Infection, of
these 1409, 61 were collected from Individuals that were 16-21Y
16

17. Evaluation of Diagnostic HIV Ag/Ab Combo Assay
17
Low Risk for HIV Infection
Population
ARCHTIECT HIV Ag/Ab
Specificity
Number of Participants 6164
HIV Ag/Ab Combo Reactive
HIV Status Positive
37
HIV Ag/Ab Combo Reactive
HIV Status Negative
14
HIV Ag/Ab Combo Nonreactive
HIV Status Positive
0
HIV Ag/Ab Combo Nonreactive
HIV Status Negative
6113
Clinical Specificity 99.77
95% Confidence Interval 99.62 to 99.88

18. Evaluation of Diagnostic HIV Ag/Ab Combo Assay
HIV Positive Population HIV p24 Ag
Sensitivity
HIV-1 Ab
Sensitivit
y
HIV-2 Ab
Sensitivity
Number of Participants 63 1003 201
ARCHITECT HIV Ag/Ab
Reactive
63 1003 201
ARCHITECT HIV Ag/Ab
Nonreactive
0 0 0
Clinical Sensitivity 100.00 100.00 100.00
95% Confidence Interval 94.31-100.00 99.63-100.00 98.18-100.00
18

19. Evaluation of Diagnostic HIV Ag/Ab Combo Assay
Pregnant Female
Population
ARCHITECT HIV
Ag/Ab
Specificity
ARCHITECT HIV
Ag/Ab
Sensitivity
Number of Participants 448 65
ARCHITECT HIV
Ag/Ab Reactive
0 65
ARCHITECT HIV
Ag/Ab Nonreactive
448 0
Clinical Specificity
95% Confidence
Interval
100.00
99.18 – 100.00
Clinical Sensitivity
95% Confidence
Interval
100.00
94.48 – 100.00
19

20. Evaluation of Diagnostic HIV Ag/Ab Combo Assay
Pediatric Population ARCHITECT HIV
Ag/Ab
Specificity
ARCHITECT HIV
Ag/Ab
Sensitivity
Number of Participants 588 64
HIV Ag/Ab Combo
Reactive
HIV Status Positive
0 64
HIV Ag/Ab Combo
Reactive
HIV Status Negative
1 0
HIV Ag/Ab Combo
Nonreactive
HIV Status Positive
0 0
HIV Ag/Ab Combo
Nonreactive
HIV Status Negative
587 0
Clinical Specificity
95% Confidence Interval
99.83
99.06 – 100.00
20

21. Evaluation of Diagnostic HIV Ag/Ab Combo Assay
Increased HIV
Risk Populations
USA HIV-2 Endemic
area
Pregnant
Females
Participants 693 513 203
Combo Reactive
HIV Status Positive
65 83 5
Combo Reactive
HIV Status
Negative
6 6 0
Combo
Nonreactive
HIV Status Positive
0 0 0
Combo
Nonreactive
HIV Status
Negative
622 424 198
21

22. References
www.fda.gov
Clinicaltrials.gov
22