Recovered file 1

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The ARCHITECT HIV Ag/Ab Combo Assay

By Payam JavanmardiAcademy of Applied Pharmaceutical

SciencesCanada, Toronto, December 2014

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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.

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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.

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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

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

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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

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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

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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

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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.

What is CMIA?

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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)

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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.

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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.

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Evaluation of Diagnostic HIV Ag/Ab Combo Assay

ClinicalTrials.gov Identifier: NCT00933933Study Type: InterventionalStudy Design: Non-Randomized, Open Label, Single group AssignmentStart Date: June 2009Study Completion Date: November 2009Study Phase: Phase 3Sponsor: Abbott Diagnostics DivisionPurpose: 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.

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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

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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)

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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

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Low Risk for HIV Infection Population

ARCHTIECT HIV Ag/Ab Specificity

Number of Participants 6164

HIV Ag/Ab Combo ReactiveHIV Status Positive

37

HIV Ag/Ab Combo ReactiveHIV Status Negative

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HIV Ag/Ab Combo Nonreactive

HIV Status Positive

0


HIV Status Negative

6113

Clinical Specificity 99.7795% Confidence Interval 99.62 to 99.88

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HIV Positive Population HIV p24 Ag

Sensitivity

HIV-1 Ab

Sensitivity

HIV-2 Ab Sensitivi

ty

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

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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 Specificity95% Confidence

Interval

100.0099.18 – 100.00

Clinical Sensitivity

95% Confidence Interval

100.0094.48 – 100.00

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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 Status Positive

0 0


HIV Status Negative

587 0

Clinical Specificity95% Confidence

Interval

99.8399.06 – 100.00

Clinical Sensitivity95% Confidence

Interval

100.0094.40 – 100.00

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Increased HIV Risk

Populations

USA HIV-2 Endemic area

Pregnant Females

Participants 693 513 203

Combo ReactiveHIV Status

Positive

65 83 5

Combo ReactiveHIV Status Negative

6 6 0

Combo NonreactiveHIV Status

Positive

0 0 0

Combo NonreactiveHIV Status Negative

622 424 198

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References

www.fda.govClinicaltrials.gov

Recovered file 1

Healthcare

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