ARCHITECT® HIV Ag/Ab Combo:

Moving HIV Diagnostics Forward in

the U.S.

Catherine Brennan, Ph.D.

Research Fellow
Infectious Diseases Research
Abbott Diagnostics

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Agenda

 ARCHITECT HIV Ag/Ab Combo Assay

 What is the Combo assay
 Performance characteristics
 Importance of detecting acute HIV infection
 Early data from US laboratories

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 ARCHITECT® HIV Ag/Ab Combo
 Chemiluminescent microparticle immunoassay for in vitro diagnostic use.
 Simultaneous qualitative detection of HIV p24 antigen and antibodies to
HIV-1 group M and group O and/or HIV-2 in human serum and plasma
(EDTA and heparin)
 Intended to be used as an aid in the diagnosis of HIV-1/HIV-2 infection,
including acute or primary infection
 An ARCHITECT HIV Ag/Ab Combo reactive result does
not distinguish between the detection of HIV-1 p24 antigen, HIV-1
antibody, or HIV-2 antibody
 May be used to aid in the diagnosis of HIV-1/HIV-2 infection in pediatric
subjects (i.e. children as young as 2 years of age) and in pregnant woman
 Not intended for use in screening blood or plasma donors. However can
be used as a blood donor screening assay in urgent situations where
traditional licensed blood donor screening assays are unavailable or their
use is impractical

ARCHITECT HIV Ag/Ab Package Insert 34-5589/R1

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ARCHITECT Instrument

 Fully-automated, random-access
(no Control brackets)
 Stat capability
 HIV Combo assay:
 29 minute time to first result
 >150 tests per hour on i2000SR
 >50 tests per hour on i1000SR

ARCHITECT HIV Ag/Ab Package Insert and ARCHITECT Operations Manual

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ARCHITECT HIV Ag/Ab Combo

 First 4th generation HIV Ag/Ab Combination assay

approved in United States; FDA approval on June
18, 2010
 >100,000 data points to evaluate
• Detection of HIV antibodies to HIV-1 group M (including diverse
subtypes), HIV-1 group O, and HIV-2
 Detection of HIV p24 antigen (diverse virus isolates,
seroconversion panels, Ab negative specimens)
 Specificity and sensitivity in low and high risk populations,
pregnant females, and pediatrics

 Overall specificity: 99.77% (95% CI: 99.62-99.88%)

 HIV antibody sensitivity:100% (95% CI: 99.63-
100.00%)
 HIV p24 Ag analytical sensitivity: 18.39 pg/mL (range
17.80-19.68 pg/mL)
ARCHITECT HIV Ag/Ab Combo Package Insert

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What is Acute Phase of HIV Infection?
Appearance of markers of HIV infection
AHI

HIV RNA
(plasma)

Anti-HIV Ab

HIV p24 Ag

0 10 20 30 40 50 60 70 80 90 100
Day post infection

 Absence of HIV specific antibodies

 Rapid rise in plasma viremia
 Acute viral syndrome: fever, rash, diarrhea, fatigue, headache –
opportunity for HIV testing
 Detect AHI by NAT or p24 antigen
Fiebig et al AIDS, 17:1871-1879 (2003)

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Why is Detection of AHI Important?

AHI makes a significant contribution to the ongoing epidemic

 May account for 15-50% of new infections

During the acute phase, substantially increased risk of transmission

 Estimated 28-fold increase compared to chronic phase
 Period of high viremia
 Virus appears to be more infectious

Individual unaware of infection status

 Often test negative

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HIV Combo Acute HIV Infection Studies

Dr J. Stekler, University of Washington, Seattle

Dr. M. Pandori, San Francisco Department of Public Health
Dr. S. Eshleman, Johns Hopkins University, Baltimore
Dr. P. Patel, CDC, Atlanta
K. Delaney, CDC, Atlanta
Dr. M. Owen, CDC, Atlanta
Dr. L. Wesolowski, CDC, Atlanta

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Acute HIV Infection Studies

Basic testing strategy:

 Specimens screened with an HIV antibody test
 All negative specimens tested by HIV NAT

Define acute HIV infection:

 Specimens detected utilizing HIV NAT

Stored specimens blinded and sent to Abbott for Combo testing

 Included HIV antibody positive, Western blot confirmed specimens and
HIV negative specimens
 Used ARCHITECT HIV Ag/Ab Combo (CE marked version; 4J27)

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Seattle Study
Stekler JD, et al, Clin Infectious Diseases 2009; 49:444-453

MSM population – high risk, frequent testing

Specimens collected at Public Health-Seattle and King County
2003-2008 specimens screened N=14,005
 HIV antibody positive N=328 (2.3%)
 HIV Ab-/RNA+ (acute) N=36 (0.3%)

NAT algorithm increased yield of HIV infection by 11%

Median time from collection to report of NAT+ result: 16-19 days

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 Seattle Combo Results

16 of 36 acute HIV Specimen HIV-1 EIA ARCHITECT HIV RNA

ID s/co Combo s/co copies/mL*
specimens available for 47 0.18 0.2 4,946
ARCHITECT HIV Combo 9 0.4 2.17 133,120
testing 10 nd 2.68 284,605
12 nd 5.09 483,329
HIV Combo detected 15 of
11 0.3 9.85 1,133,033
16 (94%)
45 0.24 10.36 637,151
HIV RNA for Combo 16 0.08 21.32 1,714,915
negative: 4,946 copies/mL 42 0.02 36.31 5,678,616
41 0.59 36.43 4,510,685
Median HIV RNA for Combo 43 0.12 42.75 5,678,616
positive: 4.5 million 44 0.25 45.87 4,510,685
copies/mL 48 0.14 54.55 8,795,135
46 0.19 80.68 22,092,380
14 0.6 101.6 26,560,883
13 0.5 108.9 6,519,924
15 0.4 463.4 >90,000,000
*RealTime HIV-1 assay performed using
residual specimen volume

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Seattle Conclusions

Extrapolation of Combo results to entire study population:

Testing Strategy % HIV Infections Detected
EIA/NAT algorithm 100
HIV Combo 99.4
1st/2nd Gen EIA 90
OraQuick Rapid 80
 The sensitivity of ARCHITECT HIV Combo greatly reduces or
eliminates the need for NAT even in a high risk, high prevalence
population.
 Combo assay could shorten time to report results. For HIV prevention
and partner notification, CDC target for time to report an HIV positive
result is <72 hours.

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ARCHITECT HIV Combo Detects Acute HIV Infections
# AHI Combo # AHI Combo
Site
tested detected
Seattle (Stekler, CID 2009; 49:444-453) 16 15 (94%)

San Francisco (Pandori, JCM 2009; 47:2639-2642) 64 57 (89%)

EXPLORE (Eshleman, JAIDS 2009; 52:121-124) 21 13 (62%)*

CDC AHI Study (Patel, Arch Int Med 2010; 170:66-74) 38 34 (89%)

CDC Rapid Study (Delaney, CROI 2009, poster 997) 17 13 (76%)*

Total 156 132 (85%)

*Site used individual NAT instead of pooled NAT

 Combo assay detected 85% of acute HIV infections

 AHI not detected by HIV Combo: 724 - 21,548 RNA copies/mL
 AHI detected by HIV Combo: 30,734 - >10,000,000 copies/mL
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ARCHITECT HIV Combo Seroconversion Sensitivity
 Based on 31 panels, Combo reduced window period a median of 7 days
relative to 3rd generation Ab assay; range 0-20 days1
Seroconversion Panel HIV 9079 (Vendor data: ZeptoMetrix Corp)
Roche Cobas ARCHITECT BioRad
Days RNA copies/mL Combo BioRad 1/2/O Unigold Multispot Oraquick HIV-1 WB
0 not detected 0.12 0.648 - - -
2 not detected 0.07 0.133 - - -
9 not detected 0.15 2.116 - - -
18 not detected 0.10 0.580 - - -
20 not detected 0.10 0.177 - - -
28 not detected 0.11 0.222 - - -
33 not detected 0.08 0.102 - - -
35 >400 0.15 0.352 - - -
40 271,000 3.58 0.287 - - - -
42 >750,000 23.85 0.119 - - - -
47 >750,000 43.06 1.065 - - - -
49 >750,000 68.68 2.679 - - - ind
55 211,000 34.81 9.689 - + - ind
57 46,300 3.78 9.949 - + - ind
62 11,000 4.13 10.239 - + - +
64 11,500 8.38 10.239 - + - +
69 21,700 12.83 10.239 - + - +
71 20,400 13.51 10.239 - + - +
76 18,800 19.63 10.239 + + + +
78 26,500 20.99 10.239 + + + +
83 18,700 24.17 10.239 + + + +
85 29,600 24.23 10.239 + + + +
90 23,800 25.15 10.239 + + + +
92 21,100 27.52 10.239 + + + +
97 15,400 29.39 10.239 + + + +
1ARCHITECT HIV Ag/Ab Combo Package Insert

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Reduction in Seroconversion Window Period

1st Gen HIV Ab

3rd Gen HIV Ab

4th Gen HIV Ag/Ab HIV RNA

(plasma)

Anti-HIV Ab

HIV p24 Ag

0 10 20 30 40 50 60 70 80 90 100
Day post infection
1st Gen Ab
35
3rd Gen Ab
22
4th Gen Ag/Ab
17
Fiebig et al, AIDS 2003; 17:1871-1879 Owen et al, J Clin Micro 2008; 46:1588-1595
Kleinman et al, Transfusion 2009; 49:2454-2489 Patel et al, Arch Int Med 2010; 170:66-74

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Erie County Medical Center Buffalo, NY:
Increased HIV Testing and Identification of AHI
 Implementation of NYS law resulted in 5-fold increase in HIV
tests performed
 Tested 3601 patients w/ ARCHITECT HIV Combo assay:
 31 confirmed HIV infections (0.9%)
 6 newly diagnosed chronic HIV infections
 1 diagnosed acute HIV infection
 Specificity: 99.92%
 AHI case:
 37 year old with acute viral syndrome came to emergency room
 Reactive for HIV: ARCHITECT HIV Combo, HIV-1 RNA
 Nonreactive for HIV: 3rd generation EIA, rapid test, western blot

Myers JB, et al., 27th Clinical Virology Symposium, May 2011, Daytona Beach FL

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ARCHITECT HIV Combo: The U.S. Experience

 Avera McKennan Hospital, Sioux Falls, SD

 3533 ARCHITECT HIV Combo tests run in 7 months
 16 confirmed HIV infections; prevalence 0.45%
 4 newly diagnosed HIV infections
 3 acute HIV infections
 48 minute average turn around time for HIV Combo result (from
time of draw)
 Specificity: 99.86%

 Dallas-Fort Worth, TX
 Tested 220 specimens from patients being screened for HIV
 Compare ARCHITECT Combo to comparator tests
 Combo detected 4 AHI not detected by comparator plus 1 recent
infection with indeterminant Western blot
Dr L Serrano, Abbott Workshop, AACC 2011.
Wians FH, et al., Labmedicine (2011) 42:523-535.

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ARCHITECT HIV Ag/Ab Combo: Conclusions
 HIV Combo detects HIV infections during the acute, recent, and
established phases of infection.
 Substantial improvement over HIV Ab immunoassays
 Sensitive Ag and Ab detection across HIV subtypes/groups
 High specificity (reduced cost associated with false-positives)
 Fully automated, random access, high through-put
 Time to first result: 29 minutes
 Early implementation of ARCHITECT HIV Combo assay has
demonstrated benefits of the assay both high and low prevalence
settings

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Publications on ARCHITECT HIV Combo
1. Ly TD, et al, J Virol Meth 2007, 143:86-94. Could the new HIV combined p24 antigen and antibody
assays replace p24 antigen specific assays?
2. Pandori MW, et al, J Clin Micro 2009, 47:2639-2642. Assessment of the ability of a fourth-generation
immunoassay for human immunodeficiency virus (HIV) antibody and p24 antigen to detect both acute
and recent HIV infections in a high risk setting.
3. Stekler JD, et al Clin Infect Dis 2009, 49:444-453. HIV testing in a high incidence population: is
antibody testing alone good enough?
4. Eshleman SH, et al, J Acquir Immune Defic Syndr 2009, 52:121-124. Detection of individuals with
acute HIV-1 infections using the ARCHITECT HIV Ag/Ab Combo assay.
5. Patel P, et al, Arch Intern Med 2010, 170:66-74. Detecting acute human immunodeficiency virus
infection using 3 different screening immunoassays and nucleic acid amplification testing for human
immunodeficiency virus RNA, 2006-2008.
6. Bischof JJ, et al AIDS 2011, 25:1927-1929. Prospective study of the ARCHITECT HIV Ag/Ab Combo
4th generation assay to detect HIV infection in STI clinics.
7. Wians FH, et al, Labmedicine 2011, 42:523-535. Evaluation of four qualitative third-generation HIV
antibody assays and the fourth-generation Abbott HIV Ag/Ab Combo test.
8. Masciotra S, et al, J Clin Virol 2011, dio:10.1016/j.jcv.2011.09.011. Evaluation of alternative HIV
diagnostic algorithm using specimens from seroconversion panels and persons with established HIV
infections.

B. Branson, CDC: APHL Webcast, Nov 15, 2011: HIV Diagnostics: New Tests and New Algorithms

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