HIV-1 Acute Infection Testing

(4th Generation) and

New Diagnostic Algorithms

Florida Consortium for HIV/AIDS Research

January 9, 2012

Berry Bennett, MPH Retrovirology Section Chief

FL. Bureau of Laboratories, FDOH berry_bennett@doh.state.fl.us

Common HIV-1 or HIV-1/2 Diagnostic Algorithm

1989……………………….

Common HIV-1 or HIV-1/2 POC Rapid Test Algorithm

Challenges with the 1989 & 1998 Diagnostic

Algorithms

• Antibody tests do not detect infection in ~10% of infected

persons at highest risk of transmission1,2

• Western blot confirmation is less sensitive during early

infection than many widely used screening tests

• Assays were FDA approved as screening or supplemental

tests in the confirmatory process, not as part of “multi-test

algorithm”.

• WB and IFA supplemental assays cannot differentiate HIV-

1 from HIV-2 infections.

1) Patel, et.al. Arch Intern Med 2010; 170:66-74

2) Stekler et.al. Clin Infect Diseases 2009; 49:444-53

Detection of HIV by Diagnostic Tests

0 1 2 3 4 5 6 7 8 9 10

Symptoms

p24 Antigen

HIV RNA

HIV EIA*

Western blot

Weeks Since Infection

*3rd generation, IgM-sensitive EIA

Modified from After Fiebig et al,

AIDS 2003; 17(13):1871-9

*2nd generation EIA

*viral lysate EIA

*4th generation, Ag/Ab Combo EIA

Characteristics & Performance of 4th Generation

Immunoassays

• Simultaneous qualitative detection of HIV-1 p24 antigen and

antibodies to HIV-1 (Groups M and O) and HIV-2 in human serum or

plasma.

• Abbott Architect HIV Ag/Ab

Combo chemiluminescent

assay (CIA), June 2010.

PI sensitivity 100% (w/95% CI

of 94.31 - 100%).

PI specificity 99.77% (w/95% CI

of 99.62 – 99.88%)

• BioRad HIV Combo Ag/Ab EIA,

July 2011.

PI sensitivity 100% (w/95% CI

of 99.7 – 100%).

PI specificity 99.87% (w/95% CI

of 99.76 – 99.93%).

Process for Developing New HIV Testing

Algorithms for the U.S.

APHL/CDC HIV Steering Committee (2006)

Algorithm Workgroups [Point of contact (POC) and Laboratory] Goal = Develop multiple acceptable HIV testing algorithms, i.e., a menu of options

APHL & NASTAD Public Health Surveys

2007 HIV Diagnostics Conference (December 5-7, Atlanta)

Preparation of the Status Report, released April 2009 at www.aphl.org/hiv/statusreport

Status Report promotion at national conferences

2010 HIV Diagnostics Conference (March 24-26, Orlando)

Release of the CLSI Guidelines1, July 2011

CDC Dear Colleague letter to Surveillance Cordinators, Nov. 18, 2011

Each state must examine their case reporting and Ryan White eligibility criteria

Ongoing data gathering: retrospective and prospective

CDC Interim Guidance anticipated by mid-2012

2012 HIV Diagnostic Conference set for Dec. 12-14, 2012

Final CDC Recommendations to follow 1 Criteria for Laboratory Testing and Diagnosis of Human Immunodeficiency Virus Infection: Approved Guidelines. Clinical and Laboratory Standards Institute, M53-A.

CDC Dear Colleague Letter to Surveillance

Coordinators – Nov. 18, 2011

“Supplemental HIV antibody tests”

need not be limited to Western Blot

or IFA. Other antibody tests are

acceptable as supplemental tests,

including some that might

alternatively be used as initial

screening tests, provided that the

screening and supplemental tests

are used together as parts of an

algorithm.

Characteristics of the Proposed HIV

Diagnostic Algorithm

• Detect acute as well as established HIV

infections

• Differentiate HIV-1 from HIV-2

• Get timely results to facilitate initiation of care -

more same day reporting

• Eliminate indeterminate and inconclusive results

whenever possible

Proposed Laboratory Algorithm

Possible HIV-1/HIV-2 Differentiation

Immunoassays

Recombinant HIV-1 gp41

Peptide HIV-1 gp41 Peptide HIV-2 gp36

Serum Control

1 gp36

2 gp160

3 gp120

4 gp41

5 gp24

Proposed HIV Point of Care Algorithm 2

A1 [HIV-1 or HIV-1/2 rapid test (Blood or oral fluid)]

A2 [HIV-1 or HIV 1/2 rapid test from a

different manufacturer (blood)]

A1-

Negative for HIV-1

and HIV-2 antibodies*

A1+

A1+ A2+

Presumptive positive for

HIV-1 or HIV-2

antibodies; requires

medical follow-up for

further evaluation and

testing

A1+ A2-

Inconclusive rapid test

result;

requires additional testing

*If using an HIV-1 only rapid test, Negative for HIV-1 antibodies only

Two Rapid Tests (A1/A2) Performed in Sequence on Blood or Oral Fluid

(A1 and A2 must be different rapid tests)

Alternative Algorithms

• Individual or pooled NAAT on seronegative specimens (primarily reflex testing)

• Traditional algorithm with supplemental NAAT option

• Algorithms for oral fluid and dried fluid spot (DFS) specimens

• “Bridge algorithms” (POC – laboratory – clinical management)

HIV Testing Algorithm Information

• HIV Testing Algorithms: A Status Report (5/2009) http://www.aphl.org/hiv/statusreport

• 2010 HIV Diagnostics Conference: http://www.hivtestingconference.org

• CLSI M53-A, Criteria for Laboratory Testing and Diagnosis of HIV-1 Infection, 2011 (Includes algorithms utilizing assays available outside the US as well as those FDA approved)

• www.journalofclinicalvirology.com/inpress (supplement issue w/ focus on data related to the proposed HIV-1/2 diagnostic algorithm)

• Updated CDC recommendations anticipated early 2012.

Thank you & Questions??