1. Annual HIV Coordinator’s Meeting 2011
4/20/2011
Annual HIV Coordinator’s Meeting 2011
PRESENTERS:
Dr. Evan Cadoff
Dr. Eugene Martin
Dr. Gratian Salaru
Joanne Corbo
UMDNJ – Robert Wood Johnson Medical School
Somerset, NJ

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

3. Gratian Salaru, MD NJ HIV
Quality Assurance
Gratian Salaru, MD
NJ HIV

4. Annual HIV Coordinators Meeting
4/20/2011
Elements of the QA Program
Optimization of Quality Control
Discordant Analysis
Discordant Trends
Rapid HIV Test Product Performance

5. Effective Quality Assurance
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
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.

6. 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
Periodic intervals
New Lot
New Shipment
Temperature for storage area
Temperature for testing area
New Operator

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

8. Annual HIV Coordinators Meeting
4/20/2011
Discordant Analysis
RWJ only
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?

9. Oral vs. Blood Discordants

10. Discordant Analysis Prelim Pos. Oraquick OQ Subtotal StatPak TOTAL
 2009
Oral
Blood
Single - Rapid 6 2 8 22 30
Rapid -Rapid 1 3 12 15 11 34 45
Prelim Pos.
Oraquick
OQ Subtotal
StatPak
TOTAL
 2010
Oral
Blood
Single - Rapid 5 1 6 12
Rapid -Rapid 11 17 29

11. Discordant Analysis 2009 2010 Discordants without follow-up 5
NUMBER
RESOLUTION   7
Discordants without follow-up
(sent to NAP:  success 1/7 found) 5
(sent to NAP:  success 1/5 found) 34
True False Pos. NEG follow-up EIA and NAT) 23 4
Confirmed Reactive by NAT and wblot at ref lab 1
Lab error
AHI likely (D43) --> initial PHEL wblot inconclusive w\ p24 only, two weeks later + NAT, bands present 3
False Neg Unigolds on Rapid-Rapids 45 29

12. Turn-Around-Time Initiative: Discordants
 2009
Cases
Average Days
Sept 27
18.9
Nov 35
14.6
Dec 45
11.3
 2010
Cases
Average Days
Annual 29
14.3

13. Surprise Lab Inspections Joanne Corbo Program Manager, NJ HIV
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
Annual HIV Coordinators Meeting
4/20/2011
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. Annual HIV Coordinators Meeting
4/20/2011
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. STATUS OF RAPID-RAPID IMPLEMENTATION
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. Disposition of Confirmed HIV+
Annual HIV Coordinators Meeting
4/20/2011
Disposition of Confirmed HIV+
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

22. Evolving Issues in RAPID TESTING
Annual HIV Coordinators Meeting
4/20/2011
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. Annual HIV Coordinators Meeting
4/20/2011
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
Annual HIV Coordinators Meeting
4/20/2011
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 RAPID TESTING ALGORITHM
Annual HIV Coordinators Meeting
4/20/2011
NJ RAPID TESTING ALGORITHM

27. Annual HIV Coordinators Meeting
4/20/2011
Diversity of sites using an RTA
NJ HIV – Marr 2011
11/17/2018

28. Annual HIV Coordinators Meeting
4/20/2011
Annual HIV Coordinators Meeting

29. February 2011 RTA Testing Volumes
Rapid Test 1
Tests
PCT
StatPak
50,262
85.4%
Oraquick Oral
5,400
9.2%
Oraquick Finger Stick
3,193
5.4%
Rapid Test 2
RTA Total Tested:
Unigold
487
 .83%
58,855

30. Verification of Prelim Positives

31. Rapid Test Algorithm - Verified Cases (394)
Rapid-Rapid Outcome
Rapid Test Algorithm - Verified Cases (394)
Rapid 1 (OQ or StatPak)
Rapid 2 (Unigold)
Number of cases
Western Blot Result +
367
Positive 1
Indeterminate (subsequently positive) 1 
Negative
(laboratory EIA negative) 25
Refused WB
R-R POS
394

32. 418 99.95% Tested Discordant Negative 50,694 Verified 391 27 50,276
Prelim Pos
418
Verified
391 27
50,276
0.77%
0.053%
99.18%
Resolved at screening
99.95%

33. Annual HIV Coordinators Meeting
4/20/2011
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
Annual HIV Coordinators Meeting
4/20/2011
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
Annual HIV Coordinators Meeting
4/20/2011
HIV ANTIBODY WINDOW is the problem
Ramp-up Viremia Doubling Time = 21.5 hrs
Peak Viremia 106 – 108 gEq/mL
Viral set-point 102 – 105 gEq/mL
WINDOW
Antibody – 22 Days
Antigen – 16 Days
Pooled NAT – 14 Days
Individual NAT – 11 Days
HIV Antibody – 3rd Generation 22 Days
P24 Ag 16 Days
Pooled NAT
14 Days
Individual NAT
11 Days
DAYS
ANTIBODY WINDOW

38. Annual HIV Coordinators Meeting
4/20/2011
Opportunity Summary
~ 55,000 new HIV infections per year in the US
Reaching and testing those at risk
~ 25% of the 850, ,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
Annual HIV Coordinators Meeting
4/20/2011
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. Kemi Alli
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
Lakisha B. 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 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. Annual HIV Coordinators Meeting
4/20/2011
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