California Clinical Laboratory Association New HIV Diagnostic Testing Algorithm November 8, 2012 Beatrice O’Keefe, Chief Laboratory Field Services California Department of Public Health

Good Morning

New HIV Algorithm Rationale for New HIV Strategy HIV Algorithm Lab Issues Challenges

Goals of the National HIV/ AIDS Strategy Reduce The Number of New HIV/AIDS Infections Increase access to care for people living with HIV/AIDS Reduce HIV related Health Disparities

“Endemic” Source: HIV/AIDS Surveillance Summary, data as of March 2011.

Continuum of HIV Care from Diagnosis to Viral Suppression 80% 62% 41% 36% 28%

California respondents Where Tested for HIV? California respondents Source: CDC Behavioral Risk Factor Surveillance System (BRFSS); telephone health survey Don’t know responses not shown; denominator is those who ever tested for HIV

1989: State of the Art Western blot ELISA

Progression of Algorithms 1989: CDC recommends 2 test algorithm T1: HIV EIA nonreactive report as HIV neg HIV Reactive perform Western blot or IFA T2: WB or IFA neg-report as neg Indeterminate-report as indeterminate Pos-report as HIV-1 Pos

1989 State of the Art

Progression of Algorithms 1992: Last Update to Algorithm T1-HIV-1/HIV-2 EIA Non-reactive-report as HIV neg Reactive-T2 WB or IFA T2-WB or IFA Neg-report as HIV neg Indeterminate-Report as indeterminate Pos-Report as HIV-1pos

Problem s Eliza + not always confirmed HIV-2 not detected Expensive follow up

HIV-2 Importance 242 cases since 1988 66% in Northeast 46% in New York City 81% born in West Africa HIV-2 cross reaction with HIV-1

Progression of HIV Viral Markers HIV RNA appears almost immediately-peaks at 28 days P24 antigen appears almost immediately - peaks at 28 days IgG comes up at 21 days, peaks at 49 days Symptoms appear at about 14 days and peak at 28 days.

New Strategy Needed 20% HIV infected persons unaware of status Approx 52% of new sexually-transmitted infections involve infected persons unaware of HIV status Includes 11% due to persons in acute phase of HIV infection Early Detection beneficial for clinical care and prevention

Strategic Plan Developed 2009 APHL & CDC status report 2010 HIV Diagnostics conference 2011 CLSI published criteria

Rationale for New Algorithm Expanded testing and earlier detection needed to reduce HIV infections New tests can detect acute & early HIV infection False positives occur with all types of initial tests WB is not able to confirm acute infections detected by 4th generation Ag/Ab tests Existing algorithm does not provide good options for resolving discrepant or false-positive results HIV-2 cross-reactivity on HIV-1 WB confuses interpretation

Multi-test Algorithm ● Test 1: Initial test Previously the screening test 3rd or 4th generation EIA or CIA ● Tests 2 & 3: Supplemental tests −WB replaced by these 2 tests ● No Confirmatory Test −Combination of test results used to determine HIV infection status

4th Generation Ag/Ab test 2 FDA approved Kits available Detects HIV-1 p24 Ag, HIV-1 and HIV-2 antibodies Reactive result: -Does not distinguish between Ag and Ab -Preliminary positive -Supplemental testing required

Advantages of HIV Algorithm HIV-1/HIV-2 assays must easier to use Timely results Reduced number of indeterminate results

Disadvantages of HIV Algorithm Cost of new HIV-1/2 Ag/Ab assays NAAT testing for low volume of specimens

State Law CCR 1230: HIV Screening Testing by Laboratories − Must use FDA approved test − Confirm all reactive or indeterminate HIV test results by the CDC confirmation protocol − Maintain a QA program that includes: Competency of testing personnel Assessment of test performance

Adoption in California CCR 17.1.2.9.1.1230 does not allow the adoption of new algorithms until published in the MMWR Delay of MMWR due to HIV 1 / 2 differentiation test (BioRad Multispot) not listed as a supplemental test in package insert. Hope for MMWR by the end of the year. (HIV Diagnostics Conference, Dec 11 – 14, 2012, Atlanta, GA.)

Status of Recommendations Clinical and Laboratory Standards Institute Criteria for Laboratory Testing and Diagnosis of Human Immunodeficiency virus Infection; Approved guideline 2011 Special Edition of Journal of Clinical Virology Http://www/sciencedirect.com/science/journal/138 66532/52/supp/S1 CDC Recommendations Summer/Fall 2012 Will parallel CLSI document

Rapid HIV 1/2 Ag-Ab Test

Those Never Tested 1.2 million have HIV 240,000 unaware of HIV status 50,000 new HIV infections each year occur from those not aware of HIV status ● At risk individuals would test more frequently if convenient test available

Home Testing

Acknowledgements Bernard M. Branson, M.D., Associate Director for Laboratory Diagnostics, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention Monica Parker, PhD, Laboratory Chief, Bloodborne Diseases, New York State Department of Health, Albany, NY Michele Owen, PhD, Laboratory Branch/Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA

Questions? Bea.Okeefe@cdph.ca.gov LFS Web site: http://cdph.ca.gov/programs/lfs