1. Annual DHAS HIV Coordinator’s Meeting 2 010 PRESENTERS: Dr. Evan Cadoff Dr. Eugene Martin Joanne Corbo UMDNJ – Robert Wood Johnson Medical School Somerset, NJ

2. Rapid HIV Testing in NJ Common Issues on Monthly Site Visits Joanne Corbo Program Manager, NJ HIV

3. Common Issues with Record Keeping Incomplete Cognition log sheets.Incomplete Cognition log sheets. Not entering their CLIS ID Number, and/or entering an incorrect CLIS ID Number.Not entering their CLIS ID Number, and/or entering an incorrect CLIS ID Number. Not writing in the comment box when entering a code – example 3 or 6. If invalid or a manufacturer error please state that and why.Not writing in the comment box when entering a code – example 3 or 6. If invalid or a manufacturer error please state that and why. Crossing out the lines on the log sheet and filling in above cross outCrossing out the lines on the log sheet and filling in above cross out Using 09 forms and rewriting over 09 to enter in the year 10 or writing outside the box.Using 09 forms and rewriting over 09 to enter in the year 10 or writing outside the box. Some sites are not faxing in the log sheets at the end of the monthSome sites are not faxing in the log sheets at the end of the month

4. Common Issues with Record Keeping (Continued) Log sheets for the month must be faxed, by the end of the month, even if the sheet is not completed.Log sheets for the month must be faxed, by the end of the month, even if the sheet is not completed. Do Not copy the log sheets.Do Not copy the log sheets. Do Not send temperature log sheets and cover pages through the Cognition faxDo Not send temperature log sheets and cover pages through the Cognition fax number number ONLY the log sheets should come through Cognition (732) 743- 3206 or (732) 743-3632. ONLY the log sheets should come through Cognition (732) 743- 3206 or (732) 743-3632. ALL OTHER forms  to (732) 235-9012 or 866-238-1469. ALL OTHER forms  to (732) 235-9012 or 866-238-1469. Some Non RWJ sites are not using the log sheets at all.!! Cognition Log sheets need to be usedSome Non RWJ sites are not using the log sheets at all.!! Cognition Log sheets need to be used

11. Rapid HIV Testing in NJ Discordant Analysis in Rapid HIV Testing Implementation of Rapid-Rapid New Directions Eugene G. Martin, Ph.D. Professor of Pathology and Laboratory Medicine UMDNJ – Robert W. Johnson Medical School

12. Topics Discordant Analysis 2009Discordant Analysis 2009 TrendsTrends Rapid Test Product PerformanceRapid Test Product Performance SpecificitySpecificity Oraquick re-formulation of manufacturing process  Improved product specificityOraquick re-formulation of manufacturing process  Improved product specificity Rapid-Rapid Initiative 2009Rapid-Rapid Initiative 2009 New Directions in Rapid TestingNew Directions in Rapid Testing Narrowing the Detection WindowNarrowing the Detection Window Acute HIV InitiativeAcute HIV Initiative New Products – Determine ComboNew Products – Determine Combo

13. Rapid HIV Testing in NJ 2009 DISCORDANT ANALYSIS

14. Trend Analysis SUMMARY Rapid HIV Discordants are rare events Many factors are involved: device, operator, experience 2009 – Dramatic decline in discordants Is it product or training? RWJ Sites ONLY

15. Discordant Analysis 2009 TOTAL StatPakOQ Blood Discordants37343 Oral Discordants8 8 TOTAL4534 11 14Non-RWJ sites Oraquick 8 Oral Discordants – Last one reported: 4/9/2009 3 Blood Discordants – Last one reported: 5/30/09 14Non-RWJ sites REPORTED

16. 2009 Discordant Analysis Prelim Pos.OraquickOQ SubtotalStatPakTOTAL OralBlood Single - Rapid6282230 Rapid -Rapid2131215 113445

17. Discordant Analysis - 2009 PCTNUMBER RESOLUTION 15.6%7 Discordants without follow-up (sent to NAP:  success 1/7 found) 75.6%34 True False Pos. neg follow- up EIA and NAT) 8.9%4 Confirmed Reactive by NAT and wblot at ref lab 1 AHI likely (D43) --> initial PHEL wblot inconclusive w\ p24 only, two weeks later + NAT, bands present 2 False Neg Unigolds on Rapid- Rapids TOTAL45

18. Turn-Around-Time Initiative: Discordants CasesAverage Days Sept2718.9 Nov3514.6 Dec45 11.3

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

20. Status of the Rapid-Rapid Initiative What is ‘Rapid-Rapid’ What is the NJ implementation process Volume/performance figures 2009 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. 2005 - Disposition of Confirmed HIV+ ProblemProblem Preliminary Positive clients fail to return for results (25.2%)Preliminary Positive clients fail to return for results (25.2%) NAP succeeds ONLY 20% of the time in locating these clientsNAP succeeds ONLY 20% of the time in locating these clients SolutionSolution Confirmatory testing on- site, same dayConfirmatory testing on- site, same day Not yet accepted by the FDANot yet accepted by the FDA In use, high prevalence areas worldwideIn use, high prevalence areas worldwide

22. Evolving Issues in RAPID TESTING Sensitivity Issues:Sensitivity Issues: Rapid HIV Tests Measures Antibodies to HIVRapid HIV Tests Measures Antibodies to HIV They DO NOT Measure HIV RNA or DNAThey DO NOT Measure HIV RNA or DNA How Sensitive are rapid HIV tests?How Sensitive are rapid HIV tests? At least as sensitive as more complex EIA technology used in hospitals and laboratoriesAt 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 problemsIn 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 algorithmSpecificity of a testing algorithm Builds upon the specificity of a testBuilds upon the specificity of a test ALL laboratory tests have aALL laboratory tests have a A sensitivity – i.e. the ability to call a true positive, positiveA sensitivity – i.e. the ability to call a true positive, positive A specificity – i.e. the ability to call a true negative, negativeA specificity – i.e. the ability to call a true negative, negative Traditionally the Western blot, improves the overall specificity of the testing algorithm.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 collected7.1% of positives could not be confirmed because specimens were not collected 25.8% did not return for results of confirmatory Western Blot25.8% did not return for results of confirmatory Western Blot ONLY 70.1% of confirmed positives got their confirmed result!!ONLY 70.1% of confirmed positives got their confirmed result!! ---------------------------------------------- ----------------------------------------------- - Western Blot confirmation has an effective sensitivity as low as 70.1%Western Blot confirmation has an effective sensitivity as low as 70.1%

25. Rapid Testing Algorithms “Rapid-Rapid” Principle:Principle: Two different immunoassays that employ different HIV antigens to search for HIV antibodies will verify the HIV result >99% of the timeTwo different immunoassays that employ different HIV antigens to search for HIV antibodies will verify the HIV result >99% of the time OutcomeOutcome Could we potentially eliminate the western blot as a confirmatory assay and substitute a second rapid HIV test???Could we potentially eliminate the western blot as a confirmatory assay and substitute a second rapid HIV test???

26. Rolling out ‘Rapid-Rapid’ VALIDATION OF THE CONCEPTVALIDATION OF THE CONCEPT SHARING THE EFFORTSHARING THE EFFORT PRESENTATION at numerous national conferences: APHA, HIV Prevention, IDSA, etc.PRESENTATION at numerous national conferences: APHA, HIV Prevention, IDSA, etc. IMPLEMENTATION DECISION: Rapid-Rapid testing at NJ HIV sites directed by RWJMS – 2009 HIV Coordinators ConferenceIMPLEMENTATION DECISION: Rapid-Rapid testing at NJ HIV sites directed by RWJMS – 2009 HIV Coordinators Conference IMPLEMENTATION PROCESS: Funding from supplemental funding from CDC, we began the roll-out in December, 2009.IMPLEMENTATION PROCESS: Funding from supplemental funding from CDC, we began the roll-out in December, 2009.

27. Validation Studies – 2004-8 Goal – To satisfy ourselves that a second, independent rapid HIV test could reliably identify false positive HIV testsGoal – To satisfy ourselves that a second, independent rapid HIV test could reliably identify false positive HIV tests 2004 – Using residual serum, we confirmed all Western blot positive sera obtained in the previous year and available at the Public Health Labs2004 – Using residual serum, we confirmed all Western blot positive sera obtained in the previous year and available at the Public Health Labs 2005-8:2005-8: Using residual sera and plasma samples to confirm that a second independent rapid HIV test could reliably identify false positive HIV tests Using residual sera and plasma samples to confirm that a second independent rapid HIV test could reliably identify false positive HIV tests

28. Rapid confirmation trial 15,923 OraQuick tests statewide15,923 OraQuick tests statewide 363 prelim positive samples to state lab for confirmatory testing363 prelim positive samples to state lab for confirmatory testing 355 Western Blot positive355 Western Blot positive 8 Western Blot negative8 Western Blot negative A second rapid test – Unigold identified all 8 false positive rapidsA second rapid test – Unigold identified all 8 false positive rapids July 1, 2004 through April 19, 2005

29. History of our RTA Selection 1.Oraquick (Oral or Fingerstick) were both in use in NJ from 2004 on. 2. StatPak was introduced in NJ at a significant number of sites 2008  INITIAL SCREENING: EITHER OraQuick (FS or O) or StatPak  VERIFICATION: Trinity Unigold 1.Two stage process to minimize: Issues of trainingIssues of training Issues of competency assessmentIssues of competency assessment Issues of required QCIssues of required QC A discordant situation in stage two would immediately bring the specimen and the client to the attention of clinicians for definitive follow-upA discordant situation in stage two would immediately bring the specimen and the client to the attention of clinicians for definitive follow-up Healthcare linkage could be achieved on the basis of two tests taking less than ½ hr.Healthcare linkage could be achieved on the basis of two tests taking less than ½ hr. 2.Since UniGold was not labeled for HIV-2 detection, we opted to initially screen by Oraquick or StatPak and verify by UniGold. If it turned out that there was a problem due to HIV-2 detection, it would have triggered central support.

30. NJ RAPID TESTING ALGORITHM

31. Rapid-Rapid Implementation PLAN:PLAN: December, 2008: 3 pilot sites began the ‘roll-out’December, 2008: 3 pilot sites began the ‘roll-out’ Sites of high prevalence first, lower prevalence laterSites of high prevalence first, lower prevalence later Policies, Procedures, Counseling Messages and Forms were completed for the entire system available before trainingPolicies, Procedures, Counseling Messages and Forms were completed for the entire system available before training Available on the ‘web’: http://www.njhiv1.orgAvailable on the ‘web’: http://www.njhiv1.orghttp://www.njhiv1.org EXPECTATIONS:EXPECTATIONS: Doesn’t eliminate Western blot confirmation, BUT allow immediate linkage to care reliably!Doesn’t eliminate Western blot confirmation, BUT allow immediate linkage to care reliably! Less than 1 in 100 would later be removed from care because of a failure to confirmLess than 1 in 100 would later be removed from care because of a failure to confirm UNKNOWNS: What will be the real world performance of a rapid test in a confirmatory setting?UNKNOWNS: What will be the real world performance of a rapid test in a confirmatory setting? Does reducing the delay really improve the linkage to care?Does reducing the delay really improve the linkage to care?

32. Training

33. 5/23/2015 NJ HIV – May, 2009 Diversity of sites using an RTA

34. Timeline - RTA Implementation

35. 2009 – NJ RTA – Testing Volumes Rapid Test 1 TestsPCT StatPak 12389 72.5% Oraquick Oral 2466 14.4% Oraquick Finger Stick 2240 13.1% Rapid Test 2 RTA Total Tested: Unigold 149.87% 17095

36. Outcome Analysis – RTA 2009 WB Results 1st Rapid Positive 2nd Rapid Positive 2nd Rapid Negative Total WB results14213110 Pct WB POS93.7% 99.2% 20.0% Pct WB Neg or Indeterminant 6.3% 0.8%80.0% Pct Refused WB 7 - 4.9%

37. Who Gets Linked to Care 74% of ‘verified’ HIV positives receive appts on the same day 26% DID NOT receive appts on the same day!! Site Specific Issues - Ongoing How to improve linkage

38. Linkage to Care - Survey It’s not too difficult in NJ to schedule a physician appointment – 6/10 sites could schedule appt 90% of time on same day as RTA positive Obtaining an appointment on the same day was more difficult --- only 3/10 sites were able to accomplish this linkage.

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

40. Rapid HIV Testing in NJ Future Directions

41. Rapid Diagnostic HIV Assays LIMITATIONS:LIMITATIONS: 1.Detects HIV antibodies, not the HIV virus 2.Western Blot Confirmation or IFA MUST BE performed. As rapid tests become more sensitive, wblot confirmation becomes more problematic.  More discordant resultsAs rapid tests become more sensitive, wblot confirmation becomes more problematic.  More discordant results 3.Client message: PRELIMINARY POSITIVE on 1 st Visit or NEGATIVE

42. Ramp-up Viremia Doubling Time = 21.5 hrs Peak Viremia 10 6 – 10 8 gEq/mL Viral set-point 10 2 – 10 5 gEq/mL WINDOW Antibody – 22 Days Antigen – 16 Days Pooled NAT – 14 Days Individual NAT – 11 Days HIV ANTIBODY WINDOW is the problem 0 10 16 22 DAYS Individual NAT 11 Days Pooled NAT 14 Days P24 Ag 16 Days HIV Antibody – 3 rd Generation 22 Days ANTIBODY WINDOW

43. Opportunity Summary 1.~ 55,000 new HIV infections per year in the US 2.Reaching and testing those at risk ~ 25% of the 850,000 - 950,000 HIV+ people in the United States are unaware of their status~ 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!!~ 30% or more who test positive for HIV by conventional testing do not receive their results!! 3.Stop the cycle by interfering with transmission More than 50% of transmission occurs in the earliest stages of an HIV infection!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.If we detect infections at the earliest stages possibility of interrupting the cycle of transmission. Once the antibody appears, infectivity is diminishingOnce the antibody appears, infectivity is diminishing 4.How to detect early infections in a simpler, more economical manner

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

45. Future – p24 Ag detection Point-of-care device

46. Detecting HIV virus before HIV antibody appears Pooled NAT on antibody negative blood Pooled NAT on antibody negative blood Blood donor facilities use to protect blood recipients since the late 1990’s.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 virusConcept – 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)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.Between 2003-7 discussions in the HIV community regarding the use of pooled NAT in high risk individuals. ExpensiveExpensive Cases eventually demonstrate antibody, so…Cases eventually demonstrate antibody, so… Why bother?Why bother? Crucial bit of information missing to justify pooled NAT!Crucial bit of information missing to justify pooled NAT!

47. The missing link More than 50% of transmission occurs in the earliest stages of an HIV infection!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.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 diminishingOnce the antibody appears, infectivity is already diminishing

48. The Question If we have the capacity to check p24 Ag with a rapid test and it narrows the window for detection by 6 days is that good enough?If we have the capacity to check 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.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 HospitalUniversity Hospital St. Michael’sSt. 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!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? What about New Jersey?

49. New Jersey HIV We’ll let you know… Next year! And Most Importantly Thanks for all you do!

50. Thanks To: RWJMS Evan Cadoff, MD Eugene Martin, Ph.D. Gratian Salaru, MD Joanne Corbo, MBA, MT (ASCP) Claudia Carron, MSN, RN Franchesca Jackson, BS (Biology) Nisha Intwala, BS, MT (ASCP) Aida Gilanchi, BS, MT Mary Ann Garrihy, BS, MT (ASCP) Patricia Riberio, BS, MT (ASCP) Lisa May Karen Williams NJDHSS/DHAS Sindy Paul, MD, MPH*Sindy Paul, MD, MPH* Linda Berezny, RNLinda Berezny, RN Maureen Wolski, BSMaureen Wolski, BS Aye Maung MaungAye Maung MaungNJDHSS/PHEL All site coordinators and counselors throughout New Jersey throughout New Jersey