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CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 1 Usefulness of a Secondary EIA Screen in a Low HIV Prevalence Population Robert J. OConnell, MD FACP.

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Presentation on theme: "CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 1 Usefulness of a Secondary EIA Screen in a Low HIV Prevalence Population Robert J. OConnell, MD FACP."— Presentation transcript:

1 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 1 Usefulness of a Secondary EIA Screen in a Low HIV Prevalence Population Robert J. OConnell, MD FACP Chief, Department of Laboratory Diagnostics and Monitoring Division of Retrovirology Walter Reed Army Institute of Research

2 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 2 Acknowledgements/Disclaimer WRAIR: SA Peel CT Bautista KN Martin NL Michael MEDCOM: DR Deuter Viromed: DL Kirkland R Sundararajan USCG: EG Schwartz MEPCOM: KP Dallen BioRad Laboratories: K Shriver The views expressed do not necessarily reflect those of the US Army, or the Department of Defense. Use of trade names is for identification only and does not imply endorsement by the US government

3 Proposed Testing Strategies for Laboratory HIV Testing Facilities Positive for HIV-1 antibodies A1 (+)A1 (-) Repeat A1 (in duplicate) A1 (++ or - +) B1 HIV-1 WB or HIV-1 IFA A1 (- -) Negative for HIV- 1 antibodies Inconclusive for HIV-1 antibodies; request redraw in 2-4 weeks; requires medical follow-up for further evaluation and testing Negative for HIV-1 antibodies A1 EIA (HIV-1) Strategy 1. HIV-1 EIA/WB/NAAT B2 Individual HIV-1 NAAT (option for initial plasma submissions) Positive for HIV- 1 antibodies and HIV-1 RNA PositiveNegativeIndeterminate Negative*Positive** * HIV-1 RNA not detected, however, a WB or IFA should be performed to confirm the absence of HIV-1 antibodies. Medical follow-up for further evaluation and testing may be required. ** It may be necessary to repeat a positive NAAT for confirmation If window period infection is suspected, refer to Acute HIV Infection Testing, Strategy 4 If HIV-2 infection is suspected, refer to HIV-2 Testing, Strategy 5 OR

4 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 4 US Army HIV Diagnostic Algorithm Genetic Systems rLAV (+)(-) Negative for HIV-1 antibodies Vironostika HIV-1 Microelisa (- -) Genetic Systems HIV-1 WB (- +) or ( + + )

5 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 5 Methods Division of Human Subjects Protection: assent to this de-identified analysis and presentation Test results (June) used to calculate number and percent of initially reactive that were not repeat reactive Final WB was the gold standard Indeterminate WBs excluded from analysis Test results from 2007 were used for ROC analysis

6 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 6 Results: Composition of Test Subjects N = 6,236,874 MEPS: Military Entrance Processing Station; USAR, U.S. Army Reserve; USANG, U.S. Army National Guard; and USCG, U.S. Coast Guard

7 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 7 Results Samples screened6,236,874 rLAV Reactive16,415 Vironostika Repeat Reactive4,142 WB Indeterminate (excluded)650 WB Positive4,009 Overall HIV-1 seroprevalence 0.06%

8 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 8 Results Overall rLAVVironostika in Duplicate Samples Screened 6,236,87416,415 Prevalence of WB+ samples 0.06%24.4% Positive Likelihood Ratio Positive predictive value 24.42% ( ) 96.79% ( )

9 Second Screen Yields 98.9% Reduction in unnecessary WBs

10 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 10 HIV-1 Prevalence by Force Component P-value < 0.001

11 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 11 HIV-1 Prevalence by Year P-value for trend < 0.001

12 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 12 rLAV-Positive Predictive Value (95% CI) by Force Component HIV-prevalence 0.07% 0.03% 0.06% 0.10% 0.05% 0.06% Positive Predictive Value (%) P-value < 0.001

13 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 13 rLAV-Positive Predictive Value (95% CI) by Year HIV-prevalence 0.06% 0.06% 0.06% 0.06% 0.07% 0.08% P-value for trend < Positive Predictive Value (%)

14 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 14 rLAV-Positive Likelihood Ratio by Year P-value for trend < 0.001

15 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 15 Repeat React-Positive Predictive Value (95% CI) by Force Component Positive Predictive Value (%) P-value = 0.073

16 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 16 Repeat React-Positive Predictive Value (95% CI) by Year Positive Predictive Value (%) P-value for Trend = 0.972

17 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 17 Repeat Reactive Positive Likelihood Ratio by Year P-value for trend = 0.972

18 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 18 rLAV-ROC analysis Cut-off-point LR+ (95% CI) PPV (95% CI) >= 1 (reference) 12.3 ( ) 32.0 ( ) >= ( ) 77.0 ( ) >= ( ) 90.7 ( ) >= 3.79** ( ) 94.0 ( ) >= ( ) 95.1 ( ) ** cut-off-point estimated by ROC analysis 2007 data only, N=512,776

19 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 19 Vironostika-ROC analysis Cut-off-point LR+ (95% CI) PPV (95% CI) >= 1 (reference) ( ) 89.7 ( ) >= ( ) 97.5 ( ) >= ( ) 98.3 ( ) >= ( ) 98.7 ( ) >= ( ) 99.1 ( ) ** cut-off-point estimated by ROC analysis 2007 data only, N=735, 16 (2.18%) discordant, all discordant are negative by WB

20 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 20 Discussion rLAV PPV driven by low prevalence Unnecessary confirmatory testing driven by screening PPV What is the effect of using two different EIAs for primary and secondary screening? Limitations: analysis of clinical testing data –Vironostika production ceased –Unknown what % of rLAV reactive/Vironostika (-/-) would have been WB positive but should be very small given high Vironostika sensitivity –WB is an imperfect gold standard

21 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 21 Discussion – Contd Two-tier approach for initial screen?: –high s/co confirmatory test –lower s/co secondary screen Increasing rLAV PPV probably multifactorial: –Slight increase in seroprevalence –Slight increase in specificity based on manufactures risk analysis of recombinant production and plate coating Performance of secondary screen in duplicate the same as in singleton.

22 CDC/APHL HIV Diagnostics Conference 5-7 Dec 07Page 22 Conclusion Secondary EIA screening substantially reduces the number of unnecessary confirmatory tests required, and should continue to be the standard for laboratory based testing algorithms in low HIV prevalence populations.


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