Annual HIV Coordinator’s Meeting 2 011

1. Annual HIV Coordinator’s Meeting2011 PRESENTERS: Dr. Evan Cadoff Dr. Eugene Martin Dr. Gratian Salaru Joanne Corbo UMDNJ – Robert Wood Johnson Medical School Somerset, NJ

2. Evan M. Cadoff, MD Interim Chairman – Dept. of Pathology UMDNJ – Robert W. Johnson Medical School introduction

3. Quality Assurance Gratian Salaru, MD NJ HIV

4. Elements of the QA Program • Optimization of Quality Control • Discordant Analysis • Discordant Trends • Rapid HIV Test Product Performance

5. Effective Quality Assurance RAPID_RAPID • Rapid-Rapid algorithms work very well but require proficient testers. • In lower incidence settings, when the second rapid is performed infrequently, possibly only a couple of times/year, competency becomes a real issue. • Reassurance of competence, while increasing the confidence of testing personnel. • Good procedure manuals, policies and document control system • Training of personnel • Quality control for the reagents and testing kits used • Competency assessment of the personnel • Proficiency testing / external proficiency evaluation • Compliance monitoring • Feedback • Overall, systematic periodic re-evaluation of these methods, policies and protocols • Collect and analyze QC and PT data

6. Periodic intervals New Operator New Lot Temperature for testing area New Shipment Temperature for storage area QC Issues • Rapid HIV testing in New Jersey utilizes three different rapid test kits. • StatPak – Oraquick - Unigold • Kits are used either in a standalone or part of a rapid-rapid testing algorithm (RTA) • All devices have an internal control that indicates adequate buffer/sample migration past the testing area, but not necessarily an indicator for sample presence

7. Quality Control • Intense effort to decrease QC usage while maintaining a strict QA process.

8. Discordant Analysis • A discordant is uncommon • Statewide decline in discordant number 20082010 in the face of significant increases in testing vol. • Although this is a sign of effective QA. What other factors might be involved? RWJ only

9. Oral vs. Blood Discordants

10. Discordant Analysis

11. Discordant Analysis

12. Turn-Around-Time Initiative: Discordants

13. Rapid HIV Testing in NJ Surprise Lab Inspections Joanne Corbo Program Manager, NJ HIV

14. Surprise Lab Inspections • NJDHSS CLIS Inspections • What to do When the Inspectors Arrive • Stay Calm • If you pass your Liaison’s monthly inspections you be fine • Show them records they ask for • Call RWJ with any questions and let us know how you did

15. Surprise Lab Inspections • What will the Inspector be looking for: • License • Temperature Logs • Test logs • Procedure Manual Signed by Lab Director • Personnel Records • Proficiency Testing Records • Standing Orders

16. RWJ Program Administrative/Logistics Issues • Submission of Data & Forms • Test logs • New Preliminary Positive Forms • New Supply Order Forms • Change In Supply Order Process • Change In Discordant Lab

17. PROJECTS & DIRECTIONS Eugene G. Martin, Ph.D. Professor of Pathology and Laboratory Medicine UMDNJ – Robert W. Johnson Medical School

18. 2011Topics • Rapid-Rapid Initiative • Acute HIV Detection in NJ • University Hospital & St. Michaels • NAT testing of antibody negative blood • New Directions in Rapid Testing • Narrowing the Detection Window • Acute HIV Initiative • New Products – Determine Combo

19. Rapid HIV Testing in NJ STATUS OF RAPID-RAPID IMPLEMENTATION

20. Status of the Rapid-Rapid Initiative • What is ‘Rapid-Rapid’ • Volume/performance figures 2010 • The CDC Surveillance Taskforce data - two rapids verify a positive HIV test 99.2% of the time • AHEAD: Efforts to recruit higher prevalence, non-RWJ sites to participate in the next phase of roll-out

21. Problem Preliminary Positive clients fail to return for results (25.2%) NAP succeeds ONLY 20% of the time in locating these clients Solution Confirmatory testing on-site, same day Not yet accepted by the FDA In use, high prevalence areas worldwide Disposition of Confirmed HIV+

22. Evolving Issues in RAPID TESTING • Sensitivity Issues: • Rapid HIV Tests Measures Antibodies to HIV • They DO NOT Measure HIV RNA or DNA • How Sensitive are rapid HIV tests? • At least as sensitive as more complex EIA technology used in hospitals and laboratories • In some cases more sensitive than the Western blot, the so-called ‘Gold Standard’ for validation. … this creates problems

23. Why run a second test? • Specificity of a testing algorithm • Builds upon the specificity of a test • ALL laboratory tests have a • A sensitivity – i.e. the ability to call a true positive, positive • A specificity – i.e. the ability to call a true negative, negative • Traditionally the Western blot, improves the overall specificity of the testing algorithm.

24. Western blot Limitations – NJ DATA • 7.1% of positives could not be confirmed because specimens were not collected • 25.8% did not return for results of confirmatory Western Blot • ONLY 70.1% of confirmed positives got their confirmed result!! • ---------------------------------------------- - • Western Blot confirmation has an effective sensitivity as low as 70.1%

25. Rapid Testing Algorithms“Rapid-Rapid” • Principle: • Two different immunoassays that employ different HIV antigens to search for HIV antibodies will verify the HIV result >99% of the time

26. NJ RAPIDTESTING ALGORITHM

27. Diversity of sites using an RTA NJ HIV – Marr 2011 4/19/2011

29. February 2011RTA Testing Volumes

30. Verification of Prelim Positives

31. Rapid-Rapid Outcome

33. 74% of ‘verified’ HIV positives receive appts on the same day • 26% DO NOT receive appts on the same day!! • LINKAGE MATTERS! • Site Specific Issues - Ongoing

34. The Next Phase • Expand Rapid-Rapid Testing • Seeking non-RWJ sites to implement Rapid-Rapid. • Goal: Linkage to care on the day HIV result is verified. • Possible Elimination of the Confirmatory Western blot • Current surveillance definition requires IFA, Western blot or RNA testing – a CDC taskforce is addressing this issue. – it matters because funding is influenced!!

35. Rapid HIV Testing in NJ Future Directions

36. Rapid Diagnostic HIV Assays • LIMITATIONS: • Detects HIV antibodies, not the HIV virus • Western Blot Confirmation or IFA MUST BE performed. • As rapid tests become more sensitive, wblot confirmation becomes more problematic.  More discordant results are inevitable

37. HIV ANTIBODY WINDOW is the problem HIV Antibody – 3rd Generation 22 Days • Ramp-up ViremiaDoublingTime = 21.5 hrs • Peak Viremia106 – 108gEq/mL • Viral set-point102 – 105gEq/mL • WINDOW • Antibody – 22 Days • Antigen – 16 Days • Pooled NAT – 14 Days • Individual NAT – 11 Days P24 Ag 16 Days PooledNAT 14 Days Individual NAT 11 Days 0 10 16 22 DAYS ANTIBODY WINDOW

38. Opportunity Summary • ~ 55,000 new HIV infections per year in the US • Reaching and testing those at risk • ~ 25% of the 850,000 - 950,000 HIV+ people in the United States are unaware of their status • ~ 30% or more who test positive for HIV by conventional testing do not receive their results!! • Stop the cycle by interfering with transmission • More than 50% of transmission occurs in the earliest stages of an HIV infection! • If we detect infections at the earliest stages possibility of interrupting the cycle of transmission. • Once the antibody appears, infectivity is diminishing • How to detect early infections in a simpler, more economical manner

39. Natural History - HIV Infection Couthino et al., Bulletin of Mathematical Biology 2001

40. Ongoing Clinical Trial of Alere Determine HIV1/2 Combo • Henry J. Austin FQHC • Dr. KemiAlli • Marylou Freund, LPN • Lenora Cheston • Maria J. Lopez • Neighborhood Health FQHC • Dr. H. Tripathi, Dr. S. Basu • Larisa Hernandez, • Maria Carrasquillo • Melissa Cornjeo • Charles Diggs • LakishaB. Ford BEGAN TWO WEEKS AGO CONCLUDES MAY 15, 2011 ALERE IS PLANNING TO SUBMIT FOR FDA CLEARANCE Between the two sites collected over 200 specimens in 2 ½ weeks!!

41. Detecting HIV virus before HIV antibody appears • Pooled NAT on antibody negative blood • Blood donor facilities use to protect blood recipients since the late 1990’s. • Concept – If you’re in the window phase, you have no antibody, you may have no p24 Ag, but you still have the virus • As of 2001, 100% of the US blood supply was tested by pooled NAT. Yield: 8 HIV antibody negative infected units in 23 million tested units. 2 p24 Ag+ units also detected. (~1:3,292,400) • Between 2003-7 discussions in the HIV community regarding the use of pooled NAT in high risk individuals. • Expensive • Cases eventually demonstrate antibody, so… • Why bother? • Crucial bit of information missing to justify pooled NAT!

42. The missing link • More than 50% of transmission occurs in the earliest stages of an HIV infection! • If we detect infections at the earliest stages, there is the possibility of interrupting the cycle of transmission. • Once the antibody appears, infectivity is already diminishing

43. The Question • If we have the capacity to detect p24 Ag with a rapid test and it narrows the window for detection by 6 days is that good enough? • We have implemented pooled NAT testing from antibody negative blood at high prevalence sites where individuals who are recently infected might logically go, if they were feeling poorly. • University Hospital • St. Michael’s • In San Francisco, last year they identified 39 individuals with Acute HIV infection, but the majority WOULD have been identified with access to p24 Ag testing! • What about New Jersey? 5 units in 3672 tests among high risk individuals (~ 13.6/10,000)!

44. Thanks To: RWJMS • Evan Cadoff, MD* • Gratian Salaru, MD* • Joanne Corbo, MBA, MT • Claudia Carron, MSN • Franchesca Jackson, BS • Nisha Intwala, MT • Patricia Ribero, MT • Mariann Garrihy, MT • Lisa May • Karen Williams All the site coordinators and counselors • NJDHSS/DHSTS • Connie F. Meyers • Sindy Paul, MD, MPH* • Steve Saunders, MS • Linda Berezny, RN • Maureen Wolski, BS • Raj Patel