Transcript Slide 1

HIV Discordant Follow-up: An Evolving Process
Gratian Salaru1, Eugene G Martin1, Sindy M Paul2, Linda Berezny2, Maureen Wolski2, Ismael Vega2, Evan Cadoff1
1University
of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School
2New Jersey Department of Health and Senior Services, Division of HIV/AIDS Services
ABSTRACT
ISSUE: Rapid HIV testing methodology has greatly improved the ‘time to result’ for the
average client being screened, and has reduced the ‘lost to follow-up’ rate from 35% to less than
1%. However, discordant results (positive rapid tests which do not confirm by Western Blot)
create considerable anxiety and ordinarily involve long delays until final resolution.
Distinguishing between exiting the HIV antibody window and a real false positive is an
important distinction in clients engaging in high risk behavior.
SETTING: In 2004, based on the original OraQuick Post-Marketing Survey, the CDC
recommended that follow-up antibody testing be performed one month after initial discordant
result was obtained. In New Jersey, follow-up testing at one month included HIV 1/2 EIA with
Western Blot if positive, and nucleic acid testing for both DNA and RNA HIV viral load.
Patients who tested negative at the one month follow-up were deemed real false positives. The
major disadvantage of this approach is the failure of patients to return one month after the initial
test.
PROJECT: In order to improve on follow-up, the NJ Notification Assistance Program (NAP)
was used to augment the outreach efforts of the testing sites. NAP had been used to reach
confirmed positives who did not return for referral to care and treatment. NAP now reaches out
to clients with discordant results who did not return for follow-up testing. NAP re-enforces the
importance of the follow-up and often obtains oral fluid for OraSure EIA and fluid Western
Blot determination. A new protocol for testing preliminary positive clients was recently
introduced. In addition to blood for Western Blot, we are now also collecting additional
specimens for follow-up testing. If the Western blot result is discordant, the additional plasma
is immediately sent for nucleic acid testing. All tests are complete by the time the client returns
for the confirmatory test results. This eliminates the one-month waiting period, and provides
much-desired final disposition to the patients. A true positive client exiting the window period
is detected up to three weeks earlier, and a false positive is resolved without the emotional
duress implied by a four week wait. Resources required for outreach to clients who fail to
return for testing are also greatly reduced. Because specimens are only sent if the results are
discordant the cost impact on the program is marginal and off-set by significant labor saving
costs.
RESULTS: Despite efforts of counselors to have clients return for follow-up, only about half of
clients with discordant results returned for follow-up testing. In 2006, NAP outreach workers
were responsible for 19% of the successful follow-up testing. But the number of clients who do
not return for testing continues to increase. The first preliminary positive client under our
newest protocol has had all results available, including nucleic acid testing, within ten days.
LESSONS LEARNED: Outreach efforts for resolving discordant results continue to be
frustrated by clients not returning for follow-up. Revised protocols can allow for more effective
and timely resolution of discordant results.
INTRODUCTION
 Rapid HIV testing improved the time to result (10 to 20 minutes depending
on method) and overall decreased the numbers of people that had an HIV test but
never received results from 35% to about 1%.
 Positive rapid HIV results are “preliminary” in currently established testing
algorithms and require additional confirmatory testing, usually performed on
serum collected by venipuncture and transported to a specialized laboratory.
 Occasionally, individuals have a preliminary positive rapid test and a
negative or indeterminate Western blot result. These criteria define a discordant
test result.
 Discordant results create considerable anxiety and ordinarily involve long
delays until final resolution.
 Distinguishing between exiting the HIV antibody window and a real false
positive is an important distinction in clients engaging in high risk behavior.
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METHODS
RESULTS
Based on initial OraQuick Post-Marketing Survey, the CDC made the
recommendation that a discordant result should be followed-up by antibody
testing a month after the initial discordant result was obtained.
 Antibody-based testing at one month consists of an HIV 1 / 2 EIA or
Western blot. Even though a rapid test is antibody-based, a repeat rapid test is
not part of the currently accepted follow-up algorithm.
 The use of an OraSure device, that collects oral fluid, is transported to a
central laboratory for Western blot testing is accepted as a follow-up method.
 In the NJHIV program, the follow-up protocols included EIA HIV 1 / 2
testing followed by Western blot if positive, but also HIV molecular testing by
PCR, most commonly RNA-based quantitative HIV RT-PCR.
 Negative results at the one month follow-up was accepted as an
indication that the original positive result was a true false-positive result.
 The major inconveniences of this protocol were the long time interval to
resolution of the case and the fact that a considerable number of patients did
not return for the scheduled one-month follow-up.
 In an effort to resolve these discordant cases, the Notification Assistance
Program, from the New Jersey Department of Health and Senior Services was
involved. NAP personnel were notified about patients who did not return for
follow-up (strict confidentiality maintained). NAP re-enforces the importance
of the follow-up testing and often obtains oral fluid for an OraSure EIA and
fluid Western blot determination.
 Despite all efforts, a significant number of clients were unreachable
(either wrong/incorrect contact information or outright refusal to cooperate
even when NAP reached a particular client).
 Two new protocols were initiated at several pilot sites to address these
shortcomings.
 One protocol called for collection of two pearl-white plasma separator
tubes (PPT) at the time of collection for the initial confirmatory Western
blot test.
 The second protocol required collection of the same pearl-white
plasma separator tubes at the time the client returns for the confirmatory
result, usually 5-7 days from the original test date.
 Since January 2006 there were a total of 162 discordant cases recorded
by NJHIV: in 2006 there were 77 cases and in 2007 (including October 2007)
there were 85 cases
 In 2006, 34% (26 clients) of the discordants were lost to follow-up.
These cases failed to return for the one month follow-up session, and include
several that did not return for the confirmatory notification either. According
to the strategy in place at that time, NAP was notified and achieved success in
19% of the follow-up cases but was not able to reach several clients or were
refused cooperation.
 In 2007, 26% (22 clients) of the discordants were lost to follow-up.
 The decreased numbers, despite increased testing volume are likely
attributable to a more efficient and aggressive follow-up strategy (Graph 1).

Current strategy
New strategy #1
New strategy #2
Positive rapid result
Positive rapid result
Positive rapid result
Confirmation WB
Confirmation WB Draw two PPT
Confirmation WB
Client notification
Client notification of discordant result
Client notification of discordant result
AND
Schedule 1 month follow-up
1 month follow-up testing
final resolution to client
Draw two PPT at time of notification
through EIA/WB and
RNA HIV viral load test
90
80
70
60
50
Total
No Follow-up
40
30
20
10
0
2006
2007
Graph 1. Discordant cases recorded by NJHIV and nofollow-up situations 2006-2007
 In 2006, using the “old” strategy the median time for resolution of a
discordant case was of 36 days with an average of 50.9 days.
 In 2007, overall, considering that new strategies were introduced only in
July of 2007, the median time for resolution was of 28 days with an average
of 35.3 days.
 At the pilot sites involved with the new strategies results were excellent:
 with strategy #1, the sites were able to reach a final resolution is as
little as 6 days from the original rapid result (range 6 to 12 days)
 with strategy #2, the final resolution was reached in as little as 9 days
(range 9 to 21 days)
 overall, including non-pilot sites, the average time for final resolution
since the implementation of the new strategies decreased to 17.9 days
through RNA HIV viral load test
Final resolution to client
through RNA HIV viral load test
Final resolution to client
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The winner in the time race is clearly strategy #1, with collection of plasma at
the time of confirmatory specimen draw. However, in trying to expand the
strategy to other sites, several problems were encountered:
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Time average
Time median
30
20
10
0
2006
2007
2007 #1
2007 #2
Graphic. 2 Please note that for the 2007#1 and 2007#2 columns, data reflects only
discordant cases included in the respective strategy. These strategies were implemented
starting in June of 2007 and include discordant cases to October of 2007
 Hardware problems:
 centrifuges, capable of accepting the plasma separator tubes
(apparently of a different design than the regular serum/red top
tubes used by the sites)
 the requirement to centrifuge the sample and separate the
plasma within two hours of collection
 freezers, required to freeze the separated plasma until picked-up
by NJHIV staff for shipment to reference laboratory
 Logistical problems:
 phlebotomist availability, on-site
 qualified personnel for centrifuge and plasma separation
 courier or staff member availability for transporting of the
specimen
 Unfortunately, the best strategy proved to also be the least feasible when
the majority of the testing sites were considered. Not many sites besides the
pilot ones had centrifuges available. While all sites had refrigerators (combo
models with freezer compartment on top) in our experience these freezer
units were unfortunately not performed enough to assure freezing of the
plasma samples within the time recommended.
CONCLUSIONS
 Outreach efforts for resolving discordant results continue to be
frustrated by clients not returning for follow-up.
 Revised protocols can allow for more effective and timely resolution of
discordant results.
 The “best” protocol, that generated the shortest turnaround time for
discordant follow-up was unfortunately impractical.
 While further evaluation is required, the currently described protocol
appears balanced in regards to costs, hardware requirements and efficacy.
Even so, cases where clients failed to return for the confirmatory result
notification continue to plague this strategy