Transcript Rapid Diagnostic HIV Testing

Validation of A
Proposed Testing
Strategy
using FDA-approved
Rapid Tests
Eugene Martin, Ph.D.
APHA 2008 Annual Meeting
San Diego, CA
October 25-29, 2008
Rapid-rapid Verification Programs
• Factors to consider:
• How is your program organized?
• Is it centrally organized or groups of independent labs?
• How much confidence do you have in each labs ability to
handle multiple assays?
• How much experience do your laboratories have in
figuring out ‘discordant results’?
• What will happen if there is a problem?
• How prevalent is HIV where you are testing? As
prevalence DECREASES…False Positives results REMAIN
constant while true positives decrease. Are you prepared
to deal with discordant results?
NJ Rapid HIV Testing
• One of the largest, most centralized rapid HIV
testing programs in the country:
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County health departments
Sexually transmitted disease clinics,
Family planning programs,
Federally qualified healthcare centers,
TB clinics,
Prisons,
Hospital-based programs – 13 ERs (8 counties),
Prenatal clinics, and
Outreach through mobile vans.
New Jersey ‘s
Rapid HIV Sites
Rapid HIV Testing in NJ
Testing Began 2003
• 23 primary sites
• 32 satellite licenses
• Western Blot
confirmation at state lab
(PHEL) in Trenton
Over 70 CTS sites,
including:
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Hospitals/EDs
FQHCs
CBOs
Health departments
Mobile vans
Prisons
UMDNJ-RWJMS/ NJ DHSS
AIDS PREVENTION GRANTEES
Primary
Satellite fixed
mobile
Pale colors indicate pending sites
AIDS Coalition of Southern New Jersey
Atlantic City Health Department
Bergen County Health Department
Burlington County Health Department
Camden AHEC
Camden County Health Department
Check-Mate
East Orange Health Department
Eric B. Chandler Health Center
FamCare
Henry J. Austin Health Center
Hope House
Horizon Health Center
Hunterdon County Health Department
Hyacinth Foundation
Martin Luther King Outreach
Morristown Memorial Hospital
Newark Community Health Center
NJCRI
Ocean County Health Department
Paterson Health Department
Plainfield Community Health Center
Proceed
Robert Wood Johnson Medical School
Trinitas Hospital
6/5/2006
Why a Centralized Program?
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STEPS
Specialized skills are centralized
Testing and processes are organized
Expenses are optimized
Problems are identified more quickly
Solutions are distributed to all:
• http://www.njhiv1.org
Why Move to Rapid Confirmation?
Disposition of Confirmed HIV + Clients
326
• Problem
350
• Preliminary Positive
clients fail to return for
results (25.2%)
• NAP succeeds ONLY 20%
of the time in locating
these clients
244
300
250
200
82
150
• Solution
47
100
11
50
0
Number
Confirmed HIV +
Referred to NAP
Result retuned to client
Found by NAP
Did Not Receive Results
• Confirmatory testing onsite, same day
Validation of a
Testing Algorithm
“Validation is the process of demonstrating
that an analytical procedure is suitable for
its intended use” – CBER
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The use of other rapid tests to confirm a rapid HIV test is not
new or novel - WHO recommends this approach for countries in
which the prevalence of HIV exceeds 10% for a number of years
• What is new and novel is using this approach in sites with 2% or
lower prevalence
Can a second rapid HIV test confirm preliminary positives
as effectively as a Western Blot?
What does any rapid test
algorithm need to do?
NEED TO DO
• Demonstrate Sensitivity
• Identify True Positives
• Not Identify False Positives
• Demonstrate Reproducibility
• Demonstrate Robustness remain unaffected by small, but
deliberate, variations in method
parameters
DATA
• Sensitivity & Specificity:
• Manufacturer’s Claims
• CDC Post Marketing Survey
• Follow-up Investigations:
• Existing confirmations
• Alternative testing
Questions for a Rapid
Testing Algorithm (RTA):
1.
Are there false negative screening tests?
2.
Can a positive client result be confirmed by a
second rapid test?
Can false positive screening tests be detected
by running a second rapid test… or a third?
What is the advantage? Disadvantage?
How can inconclusive “second-round” test results
(eg, WB vs a second rapid test) be resolved?
What is the impact on the linkage to care?
3.
4.
5.
i.e Screening test says NEG, but the client is infected.
NJ - A Two-Test Algorithm
HIV-1/2 Rapid HIV Test (Blood) STAT-Pak
Or
HIV-1/2 Rapid HIV Test (Oral) Oraquick
Unique Characteristics
• Area: New Jersey: 7,836 sq. mi> Los Angeles: 469.1 sq
mi> San Francisco: 47 sq. miles
• Population: Greater LA (2007) ~17.78 million > NJ 8.69
million > San Francisco ~ 4.18 million
• Scale: Drive End to End in NJ 3 hrs. (WE 1 ½ hours)
• A mixture of urban/suburban and rural
communities
• North – urban
• South – rural
• Many different venues perform rapid testing
Validation of the NJ
algorithm
• Three Data Sets:
• 2004
• January, 2006 – October, 2007
• 2008
2004
Ability of a Rapid to Confirm a Rapid
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ALL confirmatory specimens sent to
NJ PHEL during 8 month period:
1.
Re-ran the PHEL specimen using
Oraquick again
2. Re-ran the specimen with other rapid
tests
3. Confirmed negative result by repeat
Western blot and Viral Load
Rapid confirmation trial
July 1, 2004 through April 19, 2005
• 15,923
__OraQuick
____ _____
tests
_________
statewide
• 363
______
prelim ________
positive
_______to__
samples
state
_____
lab for
___ ___
confirmatory
testing
____________
• 355 Western Blot
positive
_______
Negative
WB Pos
Discordant
• 8 Western
______ Blot
___negative
________
• ______ ___
________
2004 NJ Data
363 Specimens
at PHEL
Orasure Oraquick
8 Negative
Western blot
8 POS
355 Positive
Western blot
Trinity UniGold
8 NEG
355 POS
7 NEG 1 POS
354 POS 1 QNS
8 NEG
340 POS
Biorad
Multispot
MedMira
Reveal
Follow-up > 2mos
6/6 neg Western blot
6/6 neg viral load
355 POS
15 sample interference
Rapid confirmation trial
2004-5 Rapid Testing Evaluation
• All testing in 2004 involved fingerstick rapid
Oraquick HIV tests
• All 8 Western Blot negative clients:
• Negative on follow-up at least 4 weeks later, by
both antibody and nucleic acid testing
• 4 of 7 tested reacted with non-viral components of
OraQuick device
• ALL were true Oraquick false positives
2004 TAKE HOME MESSAGES:
• A CLIA-waived rapid test matched Western
Blot confirmatory results in 100% of the HIV +
cases.
• Every false positive was identified by a
proposed rapid confirmation algorithm between
2004-2006!
• Potential consequences using rapid-rapid
confirmation:
• Eliminate the non-returners
• Effective sensitivity would approach 99-100%
• Counseling, contact elicitation and referral for
treatment could be Done Immediately
• In NJ, at least 200 additional HIV + individuals
would definitively know their status!!
Ability of a Rapid HIV Test to
Confirm a Rapid HIV Result
January 2006- October 2007
NJ Data Set
Jan 2006 – Oct 2007 data
BACKGROUND
• Oral HIV testing had become the predominant means of rapid HIV
testing in New Jersey.
• The rate of discordant results had increased with oral testing
METHODS
• We used retained specimens from follow-up testing of clients that were
Rapid Test (+), but Western Blot (-)
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Testing done on serum
Confirmed discordants and indeterminates (if they had follow-up).
DID NOT confirm true positives from this data set.
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Used CLIA-waived tests ONLY:
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Samples were not from the same time as the screening OraQuick.
• Repeated OraQuick on blood
• Trinity Uni-Gold
• Clearview StatPak
Follow the data!
Total Rapid HIV Testing
NJ Rapid HIV Testing 20056
• Oral Testing Introduced  More
False Positive Confirmations
Fingerstick
Oral Testing
Follow-up Information
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All follow-ups on negative Western Blot specimens were also NAAT
negative (i.e.True OraQuick false positive).
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All were "second rapid" negative.
Oral Discordants
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OraQuick followed by Blood OraQuick:
• 3 tested at CTS site on False Positives:
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2 blood negative; 1 blood positive
56 tested on follow-up blood specimen
all were blood negative
• SUMMARY: 58 specimens were truly negative; 1 specimen was positive
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Blood Discordants
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11 tested on follow-up blood specimen
• 7 negative
• 4 repeat positive
Observations
• Indeterminate Western Blot:
• 12 total:
• 4 no follow-up; 3 QNS
• 3 NAAT negative were "second rapid" negative
• 2 NAAT positive were "second rapid" positive
2008 Data
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Randomly sampled serum
specimens sent to NJ PHEL
some for confirmatory
testing; some for standard
testing. We didn’t know their
identity
Ran:
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Oraquick
UniGold
StatPak
Discordant – 2 of the 3 rapids
agreed – one did not
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UniGold twice
Oraquick three times
All
Pos
ALL Neg
UniGold
Discordant
Oraquick
Discordant
TOTAL
149
26
2
3
180
Conclusive
175
97.2%
Inconclusive
5
2.8%
Potential Issues:
Falsely negative 2nd rapid
ID
OQ80031
Oraquick
+
Trinity
Unigold
-
StatPak
+
EIA (s/co)
West. Blot
REACTIVE ALL BANDS
0.824/0.263 EXCEPT:66,17=0
Falsely positive 2nd rapid
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None using Trinity Unigold as the 2nd rapid
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Three using StatPak as the 2nd rapid
ID
OQ800131
OQ800169
OQ80032
Oraquick
+
+
+
Trinity
Unigold
NS
StatPak
+
+
+
EIA (s/co)
0.046/0.270
0.091/0.272
0.063/0.276
West. Blot
NO BANDS
NO BANDS
NO BANDS
Frequency
1:180
Conclusions:
• A second, different rapid HIV test
can confirm a preliminary rapid result
as reliably as a Western Blot.
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98% of time the conclusion will be correct
• 25% of individuals who would never have received their final
result will now!!
• New Jersey will implement rapid-rapid verification and
immediate linkage to care
• Following meetings with Department of Health it was
decided to implement rapid-rapid verification statewide
Predictive Value as a Function of Return for Results
100%
100%
Positive Predictive Value
90%
90%
80%
80%
70%
70%
60%
60%
50%
NJ - 70% get results
40%
Standard PPV
30%
New Jersy HIV
Prevalence at CTS
centers
20%
10%
0%
0%
5%
10%
HIV Prevalence
15%
Implementation
• PLAN:
• 3 pilot sites have been identified to begin the ‘roll-out’
• 1 site is up, trained and running. The other 2 - within the month
• Policies, Procedures, Counseling Messages and Forms are completed
for the entire system
• EXPECTATIONS:
• It will not eliminate Western blot confirmation, BUT it will provide
the basis for immediate linkage to care!
• Less than 1 in 100 will be later 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?
• Does reducing the delay really improve the linkage to care?
• Does post-testing counseling impact positively on prevention
messages?
RWJMS
• Evan Cadoff, MD
• Eugene Martin, Ph.D.
• Gratian Salaru, MD
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Sharon Holswade,
MBA
Franchesca Jackson,
BS
Nisha Intwala, MT
Claudia Carron, RN
Lisa May
Karen Williams
NJDHSS/DHAS
• Sindy Paul, MD, MPH*
• Linda Berezny, RN
• Maureen Wolski, BS
• Aye Maung Maung
NJDHSS/PHEL
• Kenneth Earley
• Kanjana Garcia
• Bruce Wolf, Ph.D.
Thanks To:
Site coordinators and counselors throughout New Jersey
THE END