HIV-1 Acute Infection Testing (4 th Generation) and New Diagnostic - - PowerPoint PPT Presentation

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

• f 94.31 - 100%).

PI specificity 99.77% (w/95% CI

• f 99.62 – 99.88%)
• BioRad HIV Combo Ag/Ab EIA,

July 2011. PI sensitivity 100% (w/95% CI

• f 99.7 – 100%).

PI specificity 99.87% (w/95% CI

• f 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

• r 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
• ption
• 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??