San Francisco Department of Public Health Reactivity of an Array of HIV Antibody Assays with Specimens from Acutely Infected Individuals Brian Louie, Jeffrey Klausner, Sally Liska, Teri Dowling and Mark Pandori San Francisco Department of Public Health

Presentation Goals, Objectives Describe how and why we use RNA detection to screen for HIV infection in San Francisco Illustrate the ability of different antibody tests to detect infection in people presumed to be recently infected with HIV Assess the sensitivities of all FDA-cleared HIV rapid antibody tests on acutely infected individuals

The 2006 Consensus Estimates: population size, HIV prevalence, and HIV incidence, San Francisco *2 infants not included Approximate overall prevalence in SF: 2-3%

The Diagnostic Window These values are estimates For RNA, this assumes a test with 50 copy sensitivity

RNA Testing of Pooled Specimens

From Oct. 2003 to June 2007, using this RNA testing strategy: 42 specimens were found that were screened as antibody-negative, but contained HIV RNA; approx. 13121 total tested over this time period such specimens were deemed as recently infected (“acute” or “primary” HIV infection) 22 were screened by 1st generation EIA (Vironostika), 17 were screened by OraQuick rapid test (14 fingerstick, 3 oral), and 3 were screened with a 3rd generation EIA (Bio-Rad)

22 of 42 were screened negative by 1st gen EIA (Vironostika)

17 of 42 were screened negative by OraQuick Rapid test (14 fingerstick blood, 3 oral) 1 specimen that was missed by 1st gen EIA was pos by OQ

3 of 42 were screened negative by 3rd gen EIA (Bio-Rad) So… 22+17+3 = 42 Total Specimens That were Antibody-screen Negative, But RNA + 14 of 42 were positive by This 3rd gen. EIA test and

Performance of Clearview Stat-pak with acute panel 1 of 42 was Positive by Stat-pak

Performance of Uni-gold (Trinity) with acute panel 11 of 42 were positive by Uni-gold

Performance of Multi-Spot (Bio-Rad) with acute panel 7 of 42 were Positive by Multi-spot

Performance of western blot with acute panel zero of the panel of 42 were positive by Western blot

Performance of all tests with follow-up specimens from acute panel; follow-up was 10-225 days after initial screening test, median: 20 days

Summary of sensitivity of all tests on this acute panel Follow-up specimens (10-225 days, median: 20 days after initial specimen) Initial specimens: 1st gen. EIA: 0% 3rd gen. EIA: 33% *Oraquick (p/s): 2.4% *Stat-pak: 2.4% Multi-spot: 17% *Uni-gold: 26% Western Blot: 0% 1st gen. EIA: 76% 3rd gen. EIA: 100% *Oraquick (p/s): 87% *Stat-pak: 97% Multi-spot: 100% *Uni-gold: 100% Western Blot: 79% * Low complexity, waived rapid tests

Observations: All waived (low complexity) rapid tests are at least as sensitive as 1st generation EIA on acute specimens One rapid test (Uni-gold) is notably more sensitive for acute infection than others Western Blot seems unhelpful for confirming positive antibody screening tests from acutely infected individuals

Observations Antibody “sandwich” technology based tests (3rd gen EIA and Uni-gold rapid) are more sensitive than other technologies for acutely infected individuals IgM detection ? They use higher volumes of specimen A non-sandwich test which uses a high volume of specimen was next most sensitive rapid test (Multi-spot)

Discussion: In certain high prevalence communities, the choice of which tests to use for screening must be made cautiously RNA-based tests may be the only reliable confirmation test for Ab screens in high prevalence communities

Acknowledgments Ernest Wong, Senior Microbiologist, SFDPHL Mahtab Shahkarami, Microbiologist, SFDPHL