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A Case Series of Discordant Laboratory Results with A Case Series of Discordant Laboratory Results with Statewide Rapid HIV Testing in New JerseyStatewide Rapid HIV Testing in New Jersey

Eugene G Martin, PhD1, Gratian Salaru , MD1, Sindy M Paul, MD, MPH2, Rose Marie Martin, MPH2, Maureen Wolski,BA2, Linda Berezny, BSN2, Evan M Cadoff1, MD1UMDNJ – Robert Wood Johnson Medical School and 2New Jersey Department of Health and Senior Services

AbstractBackground: A statewide case series of patients with discordant rapid HIV results at

publicly funded counseling and testing sites is described.Methods: Initial fingerstick testing by either OraQuick or OraQuick Advance was

confirmed with Vironostika HIV-1 (BioMerieux) enzyme immunoassay (EIA) and HIV-1 Western blot (Biorad). Discordant results (Oraquick positive/Western blot negative) were followed by repeat Oraquick screening at 4-6 weeks, confirmation of the original

EIA and Western blot results, collection of additional serum for hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), HIV by standard enzyme immunoassay, Epstein-Barr virus (EBV), and Rheumatoid factor (RF); collection of additional plasma for ultrasensitive, quantitative RNA determination of HIV. Demographic data were collected using the standard CDC form.

Results: Rapid testing began at a single New Jersey site on 11/1/03. Through 10/5/05, 125 sites were conducting rapid testing with 32,463 tests completed. Twenty (0.06%) patients were discordant with a preliminary positive Oraquick rapid test and a negative Western blot. Two patients refused follow-up testing. Three other patients were lost to follow-up. Nine of 10 patients tested were Oraquick positive upon re-examination 4-6 weeks later, but continued to test HIV negative by traditional EIA and Western blot. Other testing included: 12 of 12 tested were negative by ultrasensitive RNA analysis. Eight of 12 (67%) were HAV polyvalent antibody positive, 1 of 12 (8%) had acute HBV, 2 of 9 (22%) had HCV infection, 1 of 12 (8%) had RF, 12 of 12 (100%) had evidence of a distant EBV infection. No instances of an evolving HIV infection were identified.

Conclusion: Rapid testing is a reliable, reproducible screening test in publicly funded counseling and testing sites. The 0.06% observed false positive rate in sites with a rigorous QA program is acceptable.

Background – Discordant HIV Result

DEFINITION: A reactive OraQuick® rapid HIV test followed by a negative or indeterminate Western blot (WB) or immunofluorescent assay (IFA) result.

TWO TYPES OF DISCORDANTS TYPE I Positive Oraquick ®, NEGATIVE Western Blot No bands present Client is considered HIV negative and not likely to be in an HIV window. TYPE II Positive Oraquick ®, INDETERMINATE Western Blot Some bands not meeting the criteria to be declared positive are present Possibility the client is in the process of seroconverting.

What Causes Discordants?• An evolving infection – HIV screen is positive prior to traditional EIA or

Western Blot • Cross-reacting non-specific antibodies• Over-reading by testing personnel

TOTAL TESTS 11/1/03 – 10/5/05 HIV PRELIM POSITIVE WESTERN BLOT – Discordant

32,463 554 (1.7 %) 20 (3.6 % of Prelim Pos. – 0.06% Overall)

Negative Discordant WB Pos

554

PRELIM POS

20 DISCORDANT

15,570

NEGATIVE

NJ 2004 R

APID

HIV TESTIN

G

Negative Discordant WB Pos

PRELIM POS

32,463

NEGATIVE

NJ R

APID

HIV TESTIN

G

0%10%20%30%40%50%60%70%80%90%

100%

Posit

ive H

IV N

ATHAV

Poly

valen

t Abs

Acute

Hep

. BHCV

Infe

ction

Rheum

atoid

Fac

tor

Distan

t EBV

Infec

tion

Oraqu

ick S

pecif

icity

NJHIV Discordant Series11/2003 --> 10/2005

Frequency of Discordants – NJ (2003-5)

AIDS Coalition of Southern New JerseyAtlantic City Health DepartmentBergen County Health DepartmentBurlington County Health DepartmentCamden AHECCamden County Health DepartmentCheck-MateEast Orange Health DepartmentEric B. Chandler Health CenterFamCareHenry J. Austin Health CenterHope HouseHorizon Health CenterHunterdon County Health DepartmentHyacinth FoundationMartin Luther King OutreachMorristown Memorial HospitalNewark Community Health CenterNJCRIOcean County Health DepartmentPaterson Health DepartmentPlainfield Community Health CenterProceedRobert Wood Johnson Medical SchoolTrinitas Hospital

6/5/2006

UMDNJ-RWJMS/ NJ DHSS AIDS PREVENTION GRANTEES

Primary Satellite fixed mobile

Pale colors indicate pending sites

AIDS Coalition of Southern New JerseyAtlantic City Health DepartmentBergen County Health DepartmentBurlington County Health DepartmentCamden AHECCamden County Health DepartmentCheck-MateEast Orange Health DepartmentEric B. Chandler Health CenterFamCareHenry J. Austin Health CenterHope HouseHorizon Health CenterHunterdon County Health DepartmentHyacinth FoundationMartin Luther King OutreachMorristown Memorial HospitalNewark Community Health CenterNJCRIOcean County Health DepartmentPaterson Health DepartmentPlainfield Community Health CenterProceedRobert Wood Johnson Medical SchoolTrinitas Hospital

6/5/2006

UMDNJ-RWJMS/ NJ DHSS AIDS PREVENTION GRANTEES

Primary Satellite fixed mobile

Pale colors indicate pending sites

UMDNJ-RWJMS/ NJ DHSS AIDS PREVENTION GRANTEES

Primary Satellite fixed mobile

Pale colors indicate pending sites

Rapid Testing in New Jersey – NJ HIV

METHODS:• The NJ Rapid HIV Program is a large, centralized QA effort (Fig.

1)• After an initial positive Oraquick result and negative

confirmationoccurs at any site NJ HIV technical support is contacted (http://www.njhiv.org)

• At 4-6 WEEKS:– Repeat HIV by Oraquick– Venipuncture. Collect SST, white top, & purple top tube. Centrifuge

and prepare ASAP (< 4 hrs). – Ship to reference laboratory (ARUP)

• Repeat HIV1/2 EIA Qualitative HIV PCR• HIV1 Western blot Ultrasenstive Quantitative RNA

PCR• HAV (Polyvalent) Hepatitis B surf. Ag, Ab, HBcAb• HCV Ab EBV, RF,

– 4-6 weeks Independent confirmation of the original negative Western blot,

• Demographic data were collected using the standard Centers for Disease Control and Prevention counseling and testing form

CONCLUSIONS:• Between 2003-5, 20 discordant rapid HIV tests were identified

(Fig. 2). • A discordant occurs when a + Rapid HIV test fails to confirm by

confirmatory Western blot.• While evidence of distant EBV and HAV infection exist in more

than half of individuals with discordant HIV results, the frequency is similar to that in the US population (Fig. 3)

• With the growth of NJ statewide program, additional discordant results have been identified. Through September 2006, 58 additional discordants have been identified. Of these, 78% were associated with oral specimens, while 20% were associated with fingerstick specimens. A slightly lower degree of specificity is reported by the manufacturer when using oral specimen types and is apparent in NJ.

• The possibility of seasonal variation is suggested by monthly data, but remains within the manufacturer’s specificity claims.

• With the exception of a single NJ case, discordant results in 2006 have not been associated with an evolving infection as demonstrated by > 1 month follow-up utilizing qualitative DNA and quantitative RNA HIV testing, as well as HIV1/2 EIA testing.

Sp

ecim

en

Typ

e

Correlations with Disease States – NJ (2003-5)

Figure 1

Figure 2

Figure 3

NEW JERSEY DISCORDANTS - 2006

0

10

20

30

40

50

60

Jan Feb Mar Apr May Jun Jul Aug Sep YTDTotal

ORAL FINGERSTICK Venipuncture

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4

6

8

10

12

14

Jan-06 Feb-06 Mar-06 Apr-06 May-06 Jun-06 Jul-06 Aug-06 Sep-06

DISCORDANTS

Mon

th t

o

Mon

th

Figure 4

Ou

tcom

e

Figure 5

0

10

20

30

40

50

60

Jan-06 Feb-06 Mar-06 Apr-06 May-06 Jun-06 Jul-06 Aug-06 Sep-06 YTDTotal

False Pos True Pos No FollowupFigure 6