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Clinical Experience with Approved Rapid HIV Tests

Clinical Experience with Approved Rapid HIV Tests. FDA Blood Products Advisory Committee Meeting March 10, 2006. Bernard M. Branson, M.D. Associate Director for Laboratory Diagnostics Divisions of HIV/AIDS Prevention National Center for HIV, STD, and TB Prevention

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Clinical Experience with Approved Rapid HIV Tests

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  1. Clinical Experience withApproved Rapid HIV Tests FDA Blood Products Advisory Committee Meeting March 10, 2006 Bernard M. Branson, M.D. Associate Director for Laboratory Diagnostics Divisions of HIV/AIDS Prevention National Center for HIV, STD, and TB Prevention Centers for Disease Control and Prevention

  2. Outline • Background: preliminary results and PPV • Counseling message: Preliminary positive test • Post-marketing surveillance: rapid HIV tests • Rapid HIV test experience in urban programs • Investigation of false-positive oral fluid tests The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention

  3. 1989 USPHS Recommendation “The Public Health Service recommends that no positive test results be given to clients/patients until a screening test has been repeatedly reactive on the same specimen and a supplemental, more specific test such as the Western blot has been used to validate those results.” - Interpretation and Use of the Western Blot Assay for Serodiagnosis of HIV-1 Infections. MMWR R&R 1989; 38(S-7)

  4. SUDS Evaluation: STD Clinic Conventional Rapid % Protocol Protocol Change n (%) n (%) 1,160 1,493 Total Tests 29 29 (2.5) 32 (2.1) HIV Positive -16 Received Results 337 (30) 1,361 (93) HIV negative 210 23 (79) HIV positive 31 (97) 23 13 (45) Returned 30 (94) 109 10 (34) 1 (3) Required outreach -91

  5. SUDS Evaluation: STD Clinic Conventional Rapid % Protocol Protocol Change n (%) n (%) 1,160 1,493 Total Tests 29 29 (2.5) 32 (2.1) HIV Positive -16 Received Results 337 (30) 1,361 (93) HIV negative 210 23 (79) HIV positive 31 (97) 23 13 (45) Returned 30 (94) 109 10 (34) 1 (3) Required outreach -91

  6. Prevalence Site Return for Results HIV- HIV+ HIV C/T sites 1.9% 84.3% 82.1% 1.6% STD Clinics 48.1% 67.8% 2.9% Drug Treatment 70.8% 73.6% Family Planning 0.4% 76.9% 63.0% Other testing sites 2.1% 64.6% 73.2% Rapid test 93.0% 97.0% What if rapid HIV tests were used in public testing sites? Source: CDC Client Record Database, 1995

  7. Rapid Tests at All Public Sites Rapid Test Current Difference Outcome Algorithm Algorithm +8,170 (29%) Learn HIV+ 36,082 27,912 +689,325 (50%) Learn HIV- 2,074,454 1,385,129 8,301 False + screen 8,301 Total tests: 2,112,270 Prevalence: 1.6% - Update: HIV Counseling and Testing Using Rapid Tests—United States, 1995. MMWR 1998; 47:211-215.

  8. 1998: PHS Recommendation Changed “Provide preliminary positive HIV test results before confirmatory results are available in situations where tested persons benefit.”

  9. Positive Predictive Value of a Single Test Depends on Specificity & Varies with Prevalence Predictive Value, Positive Test OraQuick Reveal Single EIA Uni-Gold HIV Prevalence 10% 99% 92% 98% 97% 5% 98% 85% 96% 95% 2% 95% 69% 91% 87% 1% 91% 53% 83% 77% 0.5% 83% 36% 71% 63% 0.3% 75% 25% 60% 50% 0.1% 50% 10% 33% 25% 99.9% 99.1% 99.8% 99.7% Test Specificity (Calculated based on point-estimates in mfg package insert)

  10. Negative Predictive Value of a Single Test Depends on Sensitivity & Varies with Prevalence Predictive Value, Negative Test OraQuick Reveal Single EIA Uni-Gold HIV Prevalence 10% 99.96% 99.98% 100% 100% 5% 99.98% 99.99% 100% 100% 2% 99.99% 100% 100% 100% 1% 100% 100% 100% 100% 0.5% 100% 100% 100% 100% 0.3% 100% 100% 100% 100% 0.1% 100% 100% 100% 100% 99.6% 99.8% 100% 100% Test Sensitivity (Calculated based on point-estimates in mfg package insert)

  11. Qualitative Interpretation of Quantitative Probabilistic Expressions • Based on positive predictive value: • “Very likely” you are infected • “Somewhat likely…” • “Possible…” • “There’s a chance…”

  12. CDC’s Recommended Counseling Message • “Your preliminary test result is positive, but we won’t know for sure if you are infected with HIV until we get the results from your confirmatory test. In the meantime, you should take precautions to avoid transmitting the virus.” -HIV Counseling with Rapid Tests. http://www.cdc.gov/hiv/pubs/rt-counseling.htm

  13. Background • Oraquick Rapid HIV-1 Antibody Test • Approved for use with whole blood November 2002 • CLIA-waived February 2003 • Approved for use with oral fluid March 2004 • Approved for HIV-2 detection and name changed to “OraQuick Advance” June 2004 • CDC initiated post-marketing surveillance in 2003

  14. Postmarketing Surveillance: Aug 2004-June 2005 Median seropositivity and specificityfor 17 project areas

  15. Postmarketing Surveillance: Aug 2004-June 2005Specificity and Positive Predictive Value

  16. Rapid Test Implementation: Chicago1/1/05 – 12/31/05 • 14 Community-Based Partners • Clinics, community centers, outreach, mobile units • 4861 tests • 78 (1.6%) confirmed positive • 7 Chicago Dept of Public Health Clinics • Clinics, special testing events, outreach, jail • 3244 tests • 52 (1.6%) confirmed positive

  17. Rapid Test Implementation: Chicago • Receipt of HIV-positive test results • 64% in 2004 with conventional testing • 94% in 2005 with rapid testing • False-positives: • 7 (0.056%) of 12,395 rapid tests in 2004-2005 • Rapid testing now offered at all CDPH HIV/STD sites

  18. Rapid Test Implementation: San Francisco January – September 2005 • As of the third quarter in 2005, 46% of HIV tests were conducted using oral/fingerstick rapid tests. January – September 2005 *Note that positivity rate is higher for conventional testing, but known positives are sometimes retested to screen for access into care.

  19. Rapid Test Implementation: Los Angeles1/1/05 – 2/9/06 *Preliminary data. Data on confirmatory testing were not recorded for an additional 51 preliminary positive rapid tests that are being investigated

  20. Rapid Test Implementation: Houston1/1/05 – 11/04/05 • Note: • Conventional testing is performed in Houston Dept of Health clinics • Rapid testing is performed in community-based organizations

  21. Investigation of False-Positive Oral Fluid Rapid Tests • Press reports of false-positives: • SF Clinics Getting High False-Positive Rate on Oral HIV Test- San Francisco Chronicle 12/10/05 • False Positives from HIV Test - NY Times 12/11/05 • Facility Halts Use of Oral HIV Test– LA Times 12/16/05 • More Sites Drop Oral HIV Test- LA Times 12/20/05

  22. Sources of Data • 4 prospective studies with parallel testing of whole blood & oral fluid OraQuick, EIA, & Western blot, 2000 - 05 • Outlier analysis, 41 sites in 3 states Sept –Nov 05 • Recent testing data, NY City STD clinics, Dec 05 – Jan 06

  23. Combined Results: 4 Prospective Studies

  24. Individual Study Results

  25. Individual Study Results

  26. Minnesota Cluster, Oral Fluid False Positives - 2004 • March 2002 – March 2004: • 7 false positives, 2017 tests (Specificity 99.7%) • April 2004 – August 2004: • 16 false positives, 407 tests (Specificity 96.1%) • Follow-up study, Feb-May 2005, 9 sites in 3 states: • 0 false positives, 2,314 tests (Specificity 100%) • Case-control study could not proceed

  27. Outlier Analysis, 41 Sites in 3 Jurisdictions: False-positive Oral Fluid tests, Sept-Nov 2005 New York City New Jersey San Francisco

  28. New York City: Sept – Nov 2005

  29. San Francisco: Sept – Nov 2005

  30. New York City STD Clinics

  31. Interim Algorithm, NYC & San Francisco: Finger-stick after Reactive Oral Fluid Test OraQuick Advance Reactive with oral fluid Fingerstick Reactive Fingerstick Negative Conduct OraQuick Advance Fingerstick Counseling Message: Both rapid tests we ran today were preliminary positive. It is likely that you have HIV. To make absolutely sure, we are going to draw blood and send it to our lab so they can run confirmatory testing. The results of those tests will be ready in 1 week. In the meantime, you should assume that you are infected with HIV, and take all necessary precautions to protect your partners. Counseling Message: Although the oral rapid test we ran today was preliminary positive, the fingerstick test was negative. Because the fingerstick test is a more accurate test, it’s likely that you don’t have HIV. In order to know for sure, we need to draw blood and send it to our lab for confirmation. The results of those tests will be ready in 1 week. In the meantime, you should assume that you may be infected with HIV, and take all necessary precautions to protect your partners. Lab runs EIA, IFA/WB

  32. Positive Oral Fluid Tests with Reflex to Finger-stick, New York City STD Clinics December 22, 2005 – January 27, 2006

  33. Conclusions • Rapid HIV tests demonstrate high specificity, but as with all screening tests, false-positive tests will occur and should be expected. Confirmatory testing after a reactive test must always be performed. • More persons learn their HIV status when they receive timely results from rapid tests than with conventional HIV testing. • OraQuick specificity is slightly lower with oral fluid than with whole blood, but well above FDA’s minimum threshold (98%) with both specimen types. • Excess false-positive oral fluid tests occurred at a limited number of sites and appear to be related to unidentified site- or host-specific factors.

  34. Susan Banks (NYC) Bob Bolan (LA) Evan Cadoff (NJ) Jim Dilley (SF) Stephen Dziuban Shelley Facente (SF) Gloria Ferko (OTI) Ann Gardner (AZ) Keith Kardos (OTI) Peter Kerndt (LA) Kathleen Krchnavek (WI) Patrick Keenan (MN) Krishna Jafa (CDC) Sindy Paul (NJ) Steve Rubin (NYC) Ellen Rudy (LA) Tracey Sides (MN) Patrick Sullivan (CDC) Apurva Uniyal (LA) Laura Wesolowski (CDC) Acknowledgements

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