Impact of hiv naat in texas nine months and counting-myra brinson - texas hiv-std conference

Testing for Acute HIV Infection in Testing for Acute HIV Infection in North CarolinaNorth CarolinaBuilding The BSL-3 Facility At The

NC State Laboratory Of Public Health

Or … Stop Bugging Me!

Bath Building 306 North Wilmington Street Raleigh, NC

Myra Brinson, MT(ASCP) Myra Brinson, MT(ASCP) Virology/Serology Unit Manager Virology/Serology Unit Manager

North Carolina State Laboratory of Public HealthNorth Carolina State Laboratory of Public Health

Ph: 919-807-8835Ph: 919-807-8835

E-mail: [email protected]: [email protected]

A significant portion of all HIV infections in a US A significant portion of all HIV infections in a US routine testing population are missed by routine HIV routine testing population are missed by routine HIV Ab testing.Ab testing.

HIV-1 viral RNA is present in large copy numbers HIV-1 viral RNA is present in large copy numbers during acute infection.during acute infection.

With multistage pooling, NAATs can efficiently With multistage pooling, NAATs can efficiently diagnose acute infection with good positive predictive diagnose acute infection with good positive predictive value in low prevalence populations. value in low prevalence populations.

It is feasible for laboratories with high testing volume It is feasible for laboratories with high testing volume such as commercial and state public health labs to such as commercial and state public health labs to perform widespread screening for acute infection.perform widespread screening for acute infection.

Background

HIV-1 Testing Timeline: HIV-1 Testing Timeline:

0 1 2 3 4 5 6 7 8 9 10

Symptoms

p24 AntigenHIV RNA

HIV ELISA

Weeks Since Infection

2001 Pilot Study Design2001 Pilot Study Design All consecutive routine HIV All consecutive routine HIV

tests submitted to the NC State tests submitted to the NC State Laboratory of Public Health Laboratory of Public Health over 4 weeks from 110 publicly over 4 weeks from 110 publicly funded counseling and testing funded counseling and testing sites (CTS) [n=8505]sites (CTS) [n=8505]

Initial Ab testing - OT Initial Ab testing - OT Vironostika HIV-1 Viral Lysate Vironostika HIV-1 Viral Lysate Microelisa (State Lab)Microelisa (State Lab)

Manual pooling of Ab NR Manual pooling of Ab NR samples (State Lab)samples (State Lab)

Roche Amplicor HIV-1 Monitor Roche Amplicor HIV-1 Monitor (UNC) – Standard and US (UNC) – Standard and US

Master Pool (1:90)

Intermediate Pools (1:10)

Figure 1: Schema for pooling Ab-negative specimens

Individual Specimens Master Pool (1:90)

Intermediate Pools (1:10)

Figure 1: Schema for pooling Ab-negative specimens

Individual Specimens

2001 Pilot Study Results2001 Pilot Study Results

Acute infection: 5 per 10,000Acute infection: 5 per 10,000

Chronic infection: 44 per Chronic infection: 44 per 10,00010,000

Overall specificity: 99.99% Overall specificity: 99.99%

Estimated additional cost per Estimated additional cost per specimen: $2.01specimen: $2.01

Estimated total testing Estimated total testing costs/additional case costs/additional case diagnosed: $4,109diagnosed: $4,109

Figure 2 : Disposition of Specimens

8505 Total Specimens

38 EIA Repeat Reactive Sera

37 Newly Diagnosed WB+ Chronic Infections 1 WB Negative

v 8298 EIA negative & 5 EIA Unconfirmed Pos.

8005 Ab Neg. Specimens Pooled 5 RNA Positive

1 False + RNA Test299 Specimens

Insufficient Vol. 4 True Positive Acute Infections

12 Previously Tested HIV+

8341 Persons at Risk

152 with Data Incomplete or Questionable

2 HIV+, Status Unknown

Figure 2 : Disposition of Specimens

8505 Total Specimens

38 EIA Repeat Reactive Sera

37 Newly Diagnosed WB+ Chronic Infections 1 WB Negative

v 8298 EIA negative & 5 EIA Unconfirmed Pos.

8005 Ab Neg. Specimens Pooled 5 RNA Positive

1 False + RNA Test299 Specimens

Insufficient Vol. 4 True Positive Acute Infections

12 Previously Tested HIV+

8341 Persons at Risk

152 with Data Incomplete or Questionable

2 HIV+, Status Unknown

Pilcher CD et al, JAMA, Vol. 288/No. 2, July 10, 2002Pilcher CD et al, JAMA, Vol. 288/No. 2, July 10, 2002

Implementation of NC STAT Implementation of NC STAT

Since 2002, NC has identified AHI using NAAT Since 2002, NC has identified AHI using NAAT through the NC Screening & Tracing Active through the NC Screening & Tracing Active Transmission (STAT) programTransmission (STAT) program

Statewide collaboration to detect AHI in publicly Statewide collaboration to detect AHI in publicly funded testing sitesfunded testing sites

240,000 HIV samples/year240,000 HIV samples/year 2 to 3 week TAT for test results2 to 3 week TAT for test results Rapid notification/confirmatory testingRapid notification/confirmatory testing Rapid tracing/prospective screening of partnersRapid tracing/prospective screening of partners

The STAT Program: GoalsThe STAT Program: Goals Identify acute HIV infections in the routine HIV CTS population in NCIdentify acute HIV infections in the routine HIV CTS population in NC

Individual healthIndividual health Improve prognosis with Improve prognosis with

acute treatment?acute treatment? Early entry into care and Early entry into care and

prevention servicesprevention services Opportunity to avoid Opportunity to avoid

unwitting transmission to unwitting transmission to partnerspartners

Public HealthPublic Health Recognized previously Recognized previously

missed infectionsmissed infections Access sexual networks: Access sexual networks:

• Identify groups being Identify groups being actively infected in a actively infected in a communitycommunity

• Identify partners at high Identify partners at high proximate risk of proximate risk of infectioninfection

• IIdentify dentify individuals/groups individuals/groups actively transmitting in a actively transmitting in a communitycommunity

• Maximize impact of all Maximize impact of all interventions to reduceinterventions to reduce

transmissiontransmission

Nov. 2007

Jan. 2008

Mar. 2

005

Nov. 2003

Vironstika HIV-1 enzyme immunoassay (bioMérieux)

HIV-1/HIV-2 Plus O EIA Antibody Assay (BioRad)

NucliSENS HIV-1 QL assay

(bioMérieux)

Procleix HIV-1 assay (GenProbe)

NucliSENS EasyQ® HIV-1 assay (bioMérieux)

APTIMA HIV-1 RNA Qualitative Assay (GenProbe)

Nov. 2002

STAT Testing at NCSLPHSTAT Testing at NCSLPH

All clients presenting at approx. 135 publicly-funded All clients presenting at approx. 135 publicly-funded voluntary testing & counseling (VCT) sites are voluntary testing & counseling (VCT) sites are tested for HIV RNA using specimen poolingtested for HIV RNA using specimen pooling

Screen for antibodies to Screen for antibodies to HIV-1, HIV-2 Plus O HIV-1, HIV-2 Plus O using BioRad EIA assay using BioRad EIA assay with EVOLIS automation with EVOLIS automation

HIV antibody negative HIV antibody negative serum samples are serum samples are pooled for HIV-1 NAAT pooled for HIV-1 NAAT using Hamilton STARletusing Hamilton STARlet

Pooling SchemaPooling Schema80 HIV-1/HIV-2 Plus O Nonreactive Samples

1 B Pool (containing 120 µl x 10 A Pools) = 1200 µl 10 A Pools (containing 20 µl x 8 samples) = 160 µl

X X X X X X X X

X X X X X X X X

GenProbe APTIMA HIV-1 NAAT GenProbe APTIMA HIV-1 NAAT RNA assayRNA assay

FDA-cleared HIV-1 FDA-cleared HIV-1 RNA qualitative NAAT RNA qualitative NAAT for serum/plasmafor serum/plasma

Detects HIV-1 Detects HIV-1 subtypes (Groups M, subtypes (Groups M, N, and O)N, and O)

Analytical sensitivity: Analytical sensitivity: 30 copies/ml (98.5%)30 copies/ml (98.5%)

Clinical specificity: Clinical specificity: 99.83%99.83%

NC HIV Testing AlgorithmNC HIV Testing Algorithm

The STAT SystemThe STAT System

State Laboratory

Laboratory Identification

Disease Intervention Specialist Team

Notification, Interviews, Confirmatory Testing,

Transportation to Clinic

UNC Weekly Case-Conference

(Surveillance, Lab, DIS, UNC Evaluation Teams)

Data collection

UNC/Duke Collaborative

Free Urgent clinical evaluation

Recruitment to studies

UNC Acute HIV Program

Research Database

UNC Specimen Repository

-surveillance/research testing

North Carolina Voluntary Testing and Counseling Testing North Carolina Voluntary Testing and Counseling Testing Population 2003-2008Population 2003-2008

No. HIV Tests‡No. HIV Tests‡ ChronicChronic AcuteAcuteN N (%)(%) NN (%)(%) NN (%)(%)

TotalTotal 891,210891,210 ---- 3,7663,766 0.42%0.42% 125125 0.014%0.014%

SexSexMaleMale 279,914279,914 31%31% 2,6312,631 70%70% 9999 79%79%FemaleFemale 600,399600,399 67%67% 1,0761,076 29%29% 2626 21%21%

Median Age (Range)Median Age (Range) 2525 (0-99)(0-99) 3333 (0-84)(0-84) 2626 (16-56)(16-56)AgeAge≤≤2121 288,998288,998 32%32% 524524 14%14% 3535 28%28%>21>21 597,395597,395 67%67% 3,2263,226 86%86% 9090 72%72%

RaceRaceBlackBlack 395,825395,825 44%44% 2,5782,578 68%68% 7979 63%63%White, Non-HispanicWhite, Non-Hispanic 284,931284,931 32%32% 663663 18%18% 3434 27%27%HispanicHispanic 162,901162,901 18%18% 327327 9%9% 1010 8%8%American IndianAmerican Indian 9,5369,536 1%1% 2424 1%1% 11 1%1%MissingMissing 9,6679,667 1%1% 3434 1%1% 11 1%1%

Sexual Risk GroupSexual Risk GroupFemaleFemale 600,399600,399 67%67% 1,0761,076 29%29% 2626 21%21%Heterosexual MaleHeterosexual Male 231,575231,575 26%26% 1,0841,084 29%29% 2222 18%18%MSMMSM 26,87026,870 3%3% 1,2771,277 34%34% 7373 58%58%Unknown MaleUnknown Male 21,46921,469 2%2% 270270 7%7% 44 3%3%

‡‡From NC CTS -- number of HIV Tests performed, previous positives removed.From NC CTS -- number of HIV Tests performed, previous positives removed.Note: Table excludes 2 Acute cases identified from 11/1/2002-12/31/2002 as the number of HIV tests and chronic cases Note: Table excludes 2 Acute cases identified from 11/1/2002-12/31/2002 as the number of HIV tests and chronic cases were not available for this 2 month periodwere not available for this 2 month period



TotalTotal 891,210891,210 ---- 3,7663,766 0.42%0.42% 125125 0.014%0.014%





‡‡From NC CTS -- number of HIV Tests performed, previous positives removed.From NC CTS -- number of HIV Tests performed, previous positives removed.Note: Table excludes 2 Acute cases identified from 11/1/2002-12/31/2002 as the number of HIV tests and chronic cases Note: Table excludes 2 Acute cases identified from 11/1/2002-12/31/2002 as the number of HIV tests and chronic cases were not available for this 2 month period were not available for this 2 month period



TotalTotal 891,210891,210 ---- 3,7663,766 0.42%0.42% 125125 0.014%0.014%






North Carolina Voluntary Testing and Counseling Testing North Carolina Voluntary Testing and Counseling Testing Population 2003-2008 (cont.)Population 2003-2008 (cont.)


Site TypeSite TypeCHC/PHCCHC/PHC 17,18917,189 2%2% 109109 3%3% 33 2%2%Drug TreatmentDrug Treatment 9,9449,944 1%1% 3131 1%1% 00 0%0%Family PlanningFamily Planning 156,981156,981 18%18% 6161 2%2% 00 0%0%Field VisitField Visit 12,81912,819 1%1% 316316 8%8% 88 6%6%HIV CTSHIV CTS 62,05662,056 7%7% 872872 23%23% 2323 18%18%Hosp/PMDHosp/PMD 138138 0%0% 33 0%0% 00 0%0%OtherOther 43,99643,996 5%5% 380380 10%10% 1515 12%12%OutreachOutreach 24,04324,043 3%3% 153153 4%4% 11 1%1%Prenatal/OBPrenatal/OB 148,996148,996 17%17% 9696 3%3% 22 2%2%Prison/JailPrison/Jail 28,83628,836 3%3% 231231 6%6% 55 4%4%STDSTD 348,896348,896 39%39% 1,3861,386 37%37% 5454 43%43%TBTB 6,8726,872 1%1% 1414 0%0% 00 0%0%

MissingMissing 30,43930,439 3%3% 114114 3%3% 1414 11%11%


Initial HIV Testing Patterns of Acute Patients Initial HIV Testing Patterns of Acute Patients Stratified by EIA Generation TypeStratified by EIA Generation Type

2nd Generation2nd Generation††

(2003-2007)(2003-2007)3rd Generation3rd Generation‡‡

(2008)(2008)

NN (%)(%) NN (%)(%)

EIA(-); NAAT(+)EIA(-); NAAT(+) 8080 85%85% 1717 57%57%

EIA(+); WB(Ind.)EIA(+); WB(Ind.) 1212 13%13% 1010 33%33%

EIA(+); WB(-)EIA(+); WB(-) 22 2%2% 33 10%10%

††2nd Generation EIA: Vironstika HIV-1 (bioMérieux)2nd Generation EIA: Vironstika HIV-1 (bioMérieux)‡3rd Generation EIA: HIV-1/HIV-2 Plus O (BioRad)‡3rd Generation EIA: HIV-1/HIV-2 Plus O (BioRad)

HIV Prevalence in Voluntary Testing and HIV Prevalence in Voluntary Testing and Counseling Testing Population Stratified by Counseling Testing Population Stratified by Calendar YearCalendar Year

No. HIV Tests‡No. HIV Tests‡ ChronicChronic AcuteAcute

N N NN %% NN %%

Calendar YearCalendar Year

20032003 106,994106,994 581581 0.54%0.54% 2222 0.021%0.021%

20042004 118,885118,885 552552 0.46%0.46% 2121 0.018%0.018%

20052005 130,440130,440 590590 0.45%0.45% 2121 0.016%0.016%

20062006 145,396145,396 645645 0.44%0.44% 1515 0.010%0.010%

20072007 175,341175,341 670670 0.38%0.38% 1616 0.009%0.009%

20082008 214,154214,154 728728 0.34%0.34% 3030 0.014%0.014%

‡‡From NC CTS -- number of HIV Tests performed, previous positives removed.From NC CTS -- number of HIV Tests performed, previous positives removed.

ConclusionsConclusions

In total, 3.2% of infections identified by the STAT In total, 3.2% of infections identified by the STAT Program for Antibody-plus-RNA HIV testing Program for Antibody-plus-RNA HIV testing were AHI, which would have been missed using were AHI, which would have been missed using standard antibody based testing procedures.standard antibody based testing procedures.

The program’s success at identifying new HIV The program’s success at identifying new HIV infections has led to significant policy changes in infections has led to significant policy changes in NC, including universal reflex RNA testing for NC, including universal reflex RNA testing for EIA-negative specimens and mandatory re-EIA-negative specimens and mandatory re-testing of pregnant women in the 3testing of pregnant women in the 3rdrd trimester. trimester.

ConclusionsConclusions

The yield of AHI cases varied by site type and The yield of AHI cases varied by site type and type of antibody tests performed. Improved type of antibody tests performed. Improved sensitivity of current EIAs has resulted in a sensitivity of current EIAs has resulted in a decreased number of cases presenting as EIA (-) decreased number of cases presenting as EIA (-) and HIV-1 RNA (+). and HIV-1 RNA (+).

Decreased proportion of infected individuals in Decreased proportion of infected individuals in

NC testing population may be due to increased NC testing population may be due to increased testing among low risk populations following the testing among low risk populations following the adoption of the CDC opt-out testing in 2007.adoption of the CDC opt-out testing in 2007.

ConclusionsConclusions Testing for AHI is especially important in high risk Testing for AHI is especially important in high risk

populations such as young MSM of color for whom these populations such as young MSM of color for whom these infections would have been missed. The recent increase infections would have been missed. The recent increase in AHI detection may be due to increased testing from in AHI detection may be due to increased testing from targeted outreach programs, to increased AHI/HIV targeted outreach programs, to increased AHI/HIV education, or to increased high risk behaviors such as education, or to increased high risk behaviors such as internet partner meeting.internet partner meeting.

Although nearly 2/3 of people tested for HIV were Although nearly 2/3 of people tested for HIV were women, a smaller percentage of women are detected women, a smaller percentage of women are detected during AHI than men. Plausible explanations include during AHI than men. Plausible explanations include lower perceived risk among clients and providers, and lower perceived risk among clients and providers, and greater barriers to care and prevention services among greater barriers to care and prevention services among high-risk women.high-risk women.

Thank You!Thank You!

North Carolina State Laboratory of North Carolina State Laboratory of Public HealthPublic Health

HIV Serology Laboratory StaffHIV Serology Laboratory Staff

North Carolina Department of North Carolina Department of Health and Human ServicesHealth and Human Services

Lynne SampsonLynne Sampson

John BarnhartJohn Barnhart

Evelyn FoustEvelyn Foust

Rhonda AshbyRhonda Ashby

Peter LeonePeter Leone

University of North Carolina – University of North Carolina – Chapel HillChapel Hill

JoAnn KurucJoAnn Kuruc

Ashley MayoAshley Mayo

Cynthia GuyCynthia Guy

Joseph EronJoseph Eron

RTI InternationalRTI International

Sandra McCoySandra McCoy

University of California – University of California –

San FranciscoSan Francisco

Chris PilcherChris Pilcher

Impact of hiv naat in texas nine months and counting-myra brinson - texas hiv-std conference

Health & Medicine

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