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Methods - Testing Antibody (Ab)-plus-RNA testing reference standard: The complete algorithm, including Ab and RNA test PowerPoint Presentation
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100%. 98%. 98%. 96%. 96%. 94%. 93%. 94%. 93%. 92%. 92%. 91%. 92%. 90%. Se. 88%. 86%. 86%. 84%. 82%. 80%. 78%. 1st Gen EIA. Multi-Spot HIV 1/2. Clearview Stat-Pak. Unigold Recombigen. Oraquick Advance (Blood). Oraquick Advance (Oral Fluid). Genetic Systems HIV 1/2 Plus 0.

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slide1

100%

98%

98%

96%

96%

94%

93%

94%

93%

92%

92%

91%

92%

90%

Se

88%

86%

86%

84%

82%

80%

78%

1st Gen EIA

Multi-Spot HIV 1/2

Clearview Stat-Pak

Unigold Recombigen

Oraquick Advance (Blood)

Oraquick Advance (Oral Fluid)

Genetic Systems HIV 1/2 Plus 0

ARCHITECT HIV Ag/Ab Combo

Determine HIV-1/2 Ag/Ab Combo

992

A Clinical Study of Antigen-Antibody Rapid Testing for Acute HIV InfectionChristopher D. Pilcher1, Brian Louie2, Sheila Keating3, Mark Pandori2, Falk Fish4, Tomer Keren4, Sally Liska2, Michael P. Busch3, Frederick M. Hecht1, Jeffrey Klausner1,2 and Grant Colfax1,2from 1UCSF HIV/AIDS Division; 2SF Department of Public Health; 3Blood Systems Research Institute; 4Inverness Medical Innovations

Acute HIV infections, as a proportion of all HIV cases detected

Results

by each testing program.

The % of all HIV infected cases

Background

A key factor influencing HIV test performance, particularly in higher-risk testing sites, is the ability to detect acute HIV cases.  These cases are often negative on tests designed to detect only anti-HIV IgG

“4th generation” immunoassays (e.g., the ARCHITECT HIV Ag/Ab Combo) can detect both HIV p24 antigen and anti-HIV antibodies for earlier detection. A new rapid test (the Determine HIV-1/2 Ag/Ab Combo) is also designed to detect HIV p24 antigen and anti-HIV antibodies.

We sought to measure the potential impact of these new screening tests on the performance of real-world, public health and research testing programs in San Francisco.

Methods - Testing

Antibody (Ab)-plus-RNA testing reference standard: The complete

algorithm, including Ab and RNA tests, was used to define HIV infection.

The combined reference standard was used to determine

Sensitivity, Specificity and Positive/Negative Predictive Values for each

screening assay. Western blot was used to categorize samples as

representing acute (WB negative/indeterminate) or established (WB

positive) HIV infection.

identified that were Western blot

-

negative or indeterminate is shown.

The majority of RNA + patients found in high risk testing populations (high risk MSM, non-targeted STD clinic VCT, partner services and nPEP) were detectable by the 4th generation EIA or by the new rapid Ag/Ab combo assay, but not by 1st generation or even 3rd generation EIAs.

50%

45%

40%

40%

100%

1st Gen EIA

35%

90%

Programs with the highest yield of acute HIV infections were those targeting patients with high risk exposures

80%

Stat

-

Pak Rapid

Screening HIV

30%

+

-

70%

%

Ab

Test

Genetic Systems HIV

-

1/2

60%

25%

% Acute Infections Positive on Each Test

Plus 0

50%

20%

Determine HIV

-

1/2 Ag/

Ab

40%

Combo Rapid

30%

15%

ARCHITECT HIV Ag/

Ab

10%

Ab

Status

Pooled

RNA

20%

-

Combo

+

10%

7%

10%

6%

Confirmation

0%

5%

HIV RNA

nPEP

0%

WB

Realtime

PCR

STD Clinic

nPEP

High Risk MSM

Partner Services

High Risk MSM

STD Clinic

Partner Services

Acute HIV Diagnostic

Testing Population

-

San Francisco

-

+

Sensitivity was compared head-to-head in the high risk MSM testing population, The sensitivity estimates associated with each rapid test (light blue) and central lab immunoassay (dark blue) are shown.

Despite differences in clinical sensitivity, negative predictive values for each test to were >99.5%.

Specificity was estimated to be 100.00% for all immunoassays.

Oraquick Advance specificity was lower on oral fluid (Sp 99.86) vs. blood (99.96).

The Determine HIV Ag/Ab Combo correctly identified 80 of 81 HIV negative Options specimens, with 1 false positive result (Sp 98.9).

  • Summary
  • In practice in San Francisco testing programs, HIV screening tests differed significantly in their ability to detect HIV infections. Assays that detected acute HIV substantially increased case identification.
  • The Determine® HIV-1/2 Ag/Ab Combo, a novel point of care assay, increased detection of HIV infection compared to all existing antibody-only rapid tests. Separate signals for HIV-1 p24 antigen and HIV antibodies make immediate, point of care identification of acute cases possible. Speed and simplicity make the test appropriate for both developed and developing world settings.
  • The ARCHITECT ® HIV Ag/Ab Combo, a 4th generation immunoassay, showed even greater sensitivity for acute HIV infections. This assay could eliminate the need for pooled HIV RNA for central laboratory screening of acute HIV infections.
  • Confirmatory algorithms must be modified (e.g., to incorporate HIV RNA), as these screening tests are more sensitive than established Western blot or immuno-fluorescence assays, and have imperfect specificity.
  • The Oraquick oral fluid test device (with an estimated sensitivity of 86%) may not be appropriate for testing of high risk individuals in San Francisco.

HIV

Ab

(+)

HIV

Ab

(

-

) RNA (+)

HIV

Ab

(

-

) RNA (

-

)

Established HIV

Acute HIV

HIV Negative

Rapid Test Panel

Methods - Specimens

Testing programs were included that used both HIV antibody and HIV RNA

amplification tests in their diagnostic algorithm:

High Risk MSM, Targeted Testing Population (n=6661)— MSM at public

testing sites meeting high risk criteria (sex with HIV+, unprotected anal

intercourse, or STD)

STD Clinic Population (n=14573)— attendees to the muncipal STD clinic,

not meeting above criteria

Non-occupational Post Exposure Prophylaxis (nPEP) Population

(n=989)— patients evaluated for, or receiving, nPEP

Partner Services (PS) Testing Population (n=173)— sexual or

needlesharing partners to newly diagnosed HIV+

Acute HIV Diagnostic Testing Population (n=1114; 1998-2008)— patients

screened for having acute HIV by the UCSF Options study based on acute

retroviral symptoms and/or high risk exposure.

Central Lab Test Panel

Oraquick

Advance

3

Gen EIA (

Gen Systems

HIV

½

Plus O)

rd

Clearview

Stat

-

Pak

4

Gen IA (Abbott ARCHITECT HIV Ag/

Ab

Combo)

th

Unigold

Recombigen

Western Blot (

Biorad

Genetic Systems)

Multispot

HIV 1/2

Determine HIV

1/2 Ag/

Ab

Combo

Head to head comparative performance evaluation: Acute specimens (RNA+, WB- or indeterminate) were submitted to Rapid Test and Central Lab panel tests. Sensitivity and Negative Predictive Values (NPV) were calculated for each panel test, assuming 100% detection of WB positive specimens.

Determine HIV-1/2 Ag/Ab Combo: Rapid Test Readout

Acknowledgements

The work was supported by R01- MH068686; we are grateful to Shelley Facente for analysis and to John Hackett, Jr. for providing 4th generation IA data, previously submitted for publication (Pandori MW, Hackett Jr., Louie B, et al., as “Assessment of the Ability of a Fourth Generation Immunoassay for HIV Antibody and p24 Antigen to Detect both Acute and Recent HIV Infection in a High-Risk Setting.”)