Medical devices; architect hiv ag:ab combo assay

The ARCHITECT HIV Ag/Ab Combo Assay

By Payam Javanmardi

Academy of Applied Pharmaceutical Sciences

Canada, Toronto, December 2014

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On June 21, 2010 FDA approved the first Diagnosticassay to detect both HIV Ag and Abs to HumanImmunodeficiency Virus.

This assay approved for use as an aid in thediagnosis of HIV-1/HIV-2 infection in adultsincluding pregnant women.

It is also the first assay for use as an aid in thediagnosis of HIV-1/HIV-2 infection in children asyoung as two years old.

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The ARCHITECT HIV Ag/Ab combo assay is notintended 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 blooddonor screening tests are unavailable or their use is

impractical.

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

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The sensitivity of a clinical test refers to the ability of thetest to correctly identify those patients with the disease.

Sensitivity= TP/ TP+FN

The Specificity of a clinical test refers to the ability of thetest to correctly identify those patients without the disease.

Specificity= TN/ TN+FP

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The ARCHITECT HIV Ag/Ab combo assay is aChemiluminescent Microparticle Immunoassay (CMIA)for the simultaneous qualitative detection of HIV gp24Ag and Antibodies to HIV-1/HIV-2 in Human serum or

plasma

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An Immunoassay technique in which the microparticlebound antigen or antibody is labeled with a moleculecapable of emitting light during a chemical reaction.

This light is used to measure the formation of the Ag-Abcomplex.

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What is CMIA?

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.

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: 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. 11


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 ofARCHITECT HIV Combo in increased HIV High RiskPopulations

Recruitment Details:

All specimens collected under separate collection Protocols orobtained from specimens Supplier;

HIV Ag +/ HIV-1 Ab+ samples collected from Individuals atRisk for HIV Infection in the USA

HIV-2 Ab+ samples collected from HIV-2 endemic area(IvoryCoast)

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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 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


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

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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 Specificity

95% Confidence

Interval

100.00

99.18 – 100.00

Clinical Sensitivity

95% Confidence

Interval

100.00

94.48 – 100.0017


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

Clinical Sensitivity 100.00

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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

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References

www.fda.govClinicaltrials.gov

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