Presentation on theme: "HIV Diagnostics and A New Testing Algorithm Lorna Seybolt, M.D., M.P.H. Louisiana State University Health Sciences Center Children’s Hospital New Orleans."— Presentation transcript:
HIV Diagnostics and A New Testing Algorithm Lorna Seybolt, M.D., M.P.H. Louisiana State University Health Sciences Center Children’s Hospital New Orleans June 23, 2012
Objectives Describe the evolution of HIV testing from the beginning of the epidemic to the currently available tests Delineate the proposed new testing algorithm Review recent studies supporting the use of the new algorithm
Considerations ~half of US adults have been tested Not much change since 2004 ~20% of 1 million infected don’t know ~1/3 have AIDS diagnosis within 1 year of testing positive 40,000 new infections/yr 25% unaware 54% new infections 75% aware 46% new infections
FDA Timeline 1985 ELISA test kit for antibodies 1987 Western Blot 1989 Virus antigens (HIV-1)
FDA Timeline 1990 Recombigen HIV-1 EIA antibody detection For high volume sites Novopath HIV-1 immunoblot test for detection of antibody to individual proteins 1991 Combo test to detect HIV 1 and 2 antibodies
FDA Timeline 1992 SUDS HIV-1 10 minute diagnostic test kit 1994 Non blood-based collection kit Utilizes oral fluid for detection of HIV-1 antibody
FDA Timeline 1996 March Coulter HIV-1 (p24 antigen) May Confide HIV Testing System Can be used at home, purchased OTC 3 components OTC home blood collection kit HIV antibody testing at certified lab Results, counseling, referral
FDA Timeline 1996 June AMPLICOR HIV-1 Monitor Test NAAT for quantitation HIV-1 RNA in plasma June HIV-1 WB confirmatory test for oral collection system August Urine-based test (ELISA)
FDA Timeline 1998 WB for urine specimen testing 1999 Supplement to AMPLICOR HIV-1 Monitor Extend LLQ from 400 50 copies/ml
FDA Timeline 2001 September First NAT systems to screen plasma donors for HIV and HCV September TrueGene HIV-1 Genotyping Kit Open Gene DNA Sequencing System Identification of drug resistance November NucliSens HIV-1 QT For prognostic assessment and monitoring
FDA Timeline 2002 September VERSANT HIV-1 RNA 3.0 Assay bDNA (quantitation) November OraQuick Rapid HIV-1 Antibody Test First rapid diagnostic test kit Results in 20 min, drop of blood No specialized equipment In 2003 test CLIA waived
OraQuick Rapid HIV 1/2 Antibody Oral fluid, plasma, whole blood (fingerstick, venipuncture) CLIA waived for all but plasma OraSure HIV-1 Oral Specimen Collection Device Collects oral fluid for lab-based EIA screening tests OraSure HIV-1 WB Kit Confirmatory assay for specimens collected with oral collection device
FDA Timeline 2004 March OraSure Rapid Test approved for detection of HIV-2 March Oral fluid samples, results in 20 min OraQuick Rapid HIV-1 Antibody Test (plasma for HIV-1/2) June CLIA waiver OraQuick ADVANCE Rapid HIV- 1/2 Antibody Test (oral fluid) December Multispot HIV-1/HIV-2 Rapid Test Discriminatory test
FDA Timeline 2005 Meeting to discuss home-use rapid HIV test kits OraQuick ADVANCE Rapid HIV-1/2 Antibody Test, oral fluid 2006 APTIMA HIV-1 RNA Qualitative Assay To detect primary HIV infection Can also be used for confirmation ADVIA Centaur 3 rd generation format
FDA Timeline May 2007 Abbott Real Time HIV-1 Assay RT-PCR for quantitation 40-10 million copies/ml AmpliPrep/COBAS TaqMan HIV-1Test Automated PCR for quantitation Procleix Ultrio Assay Qualitative NAT to screen blood
FDA Timeline 2008 March VITROS Anti-HIV-1/2 (3 rd gen) Donor screening December COBAS TaqScreen MPX Test First to detect HIV-2 and HIV-1 group O Donated plasma
FDA Timeline 2009 Avioq HIV-1 Microelisa Oral fluid, DBS 2010 Rapid INSTI HIV-1 60 sec antibody test Abbott Architect 4 th gen Ag/Ab Combo 2011 Bio-Rad GS HIV Ag/Ab Combo
Where Do Your Specimens Go?
What Happens When They Get There? ???
1927-1945 - Silent Generation or Traditionalists 1946-1964 - Baby Boomers 1965-1983 - Gen X or the Busters 1984- 2002 - Gen Y or the Millennials 2003- Current Gen Z or the Digital Generation
Arch Intern Med. 2010;170(1):66-74
Who Is This Girl? And Why Is She Famous?
Available Tests Conventional blood test 1 st, 2 nd, 3 rd, 4 th generation EIA Conventional oral fluid test OraSure (collection device) Avioq (used with specimens collected with OraSure device)
Available Tests Rapid tests OraQuick Advance Rapid HIV-1/2 Antibody Test Reveal Rapid HIV-1 Antibody Test Uni-Gold Recombigen HIV Test Multispot HIV-1/HIV-2 Rapid Test Clearview HIV 1/2 Stat Pak Clearview Complete HIV 1/2
Available Tests Home tests HomeAccess HIV-1 Test System
Available Tests Urine test Calypte ???
Available Tests Urine test Maxim HIV-1 Urine EIA Cambridge Biotech Urine HIV-1 WB
Limitations of Current Algorithm Newer screening tests are more sensitive than WB for detecting early infection New 4 th generation Ag/Ab tests detect infection during early, antibody negative, highly infectious stage Misdiagnosis of HIV-2 infections as HIV- 1 (60%)
Arch Intern Med. 2010;170(1):66-74
J Acquir Immune Defic Syndr 2010;55:S102–S105
False Positive OR False Negative ???
Paradigm Shift ???
Proposed New Diagnostic Algorithm
J Acquir Immune Defic Syndr 2010;55:S102–S105
Evidence for New Algorithm
Performance of an alternative laboratory-based algorithm for HIV diagnosis in a high-risk population High risk persons Comparison of multi IA’s and rapid tests with NAAT vs WB Correct classification of all with few needing NAAT Journal of Clinical Virology 52S (2011) S5– S10
Evaluation of an alternative HIV diagnostic algorithm using specimens from seroconversion panels and persons with established HIV infections Acute and established infections 3 rd and 4 th gen IA’s, rapid tests, NAAT, and WB Improved sensitivity for detecting acute infection while maintaining ability to detect established infection Journal of Clinical Virology 52S (2011) S17– S22
Evaluation of an alternative supplemental testing strategy for HIV diagnosis by retrospective analysis of clinical HIV testing data Retrospective analysis of test results to compare algorithms 38,257 specimens Proposed algorithm outperformed current More sensitive for detecting HIV-1 infection, greater number definitive results, detected HIV-2 more efficiently Journal of Clinical Virology 52S (2011) S35– S40
Comparison of Multispot EIA with Western blot for confirmatory serodiagnosis of HIV Comparison of 3 rd gen IA followed by Multispot vs WB 8,760 specimens Detected additional 14 HIV-1 infections, differentiated 26 HIV-1 WB positives as HIV-2, detected additional 12 HIV-2 infections Journal of Clinical Virology 52S (2011) S41– S44
Performance of an alternative laboratory-based algorithm for diagnosis of HIV infection utilizing a third generation immunoassay, a rapid HIV-1/HIV-2 differentiation test and a DNA or RNA-based nucleic acid amplification test in persons with established HIV-1 infection and blood donors Evaluation of 3 rd gen IA and Multispot followed by NAAT for IA positive/MS negative HIV infected, not on therapy HIV uninfected blood donors Algorithm had high sensitivity and specificity in specimens from HIV infected and uninfected (blood donors) Journal of Clinical Virology 52S (2011) S45– S49
Proposed Algorithm With current HIV-1/2 differentiation tests turnaround time is less than that with WB Resolve most positive specimens with only 2 tests RNA test only for those antibody negative specimens likely to represent acute infection
Proposed Algorithm Decrease cost Decrease turn around time Increase detection of acute infections Increase sensitivity for detecting acute infections while maintaining ability to detect established infections Reduce or eliminate misclassification of HIV-2 infections
What’s Next? Revision of HIV surveillance case definition Feb 2012—consultation convened by CDC Recommendations regarding testing algorithms, HIV-2, ‘Stage 0’ infection To be presented to CSTE at annual meeting June 2012 Anticipate MMWR later in 2012
What’s Next? Rapid 4 th generation test HIV 1/2 rapid line assay POC fingerstick rapid test Viral load CD4
Ability to Detect Infection Earlier More Detected Earlier
Selected References Journal of Clinical Virology : 2011 Supplement – www.journalofclinicalvirology.com MMWR July 21,1989 – Volume 38, Supplement No. 7 Henry J. Kaiser Family Foundation – HIV/AIDS Policy – www.kff.org J Acquir Immune Defic Syndr 2010;55:S102-S105 – The Future of HIV Testing, Bernard M. Branson Expert Rev Anti Infect Ther 2010;8(6):631-633 – 2010 HIV Diagnostics Conference Summary of the 2012 Consultation of Revision of the HIV Surveillance Case Definition – http://www.cdc.gov/hiv/resources/reports/pdf/HIV_Case_Def_Consult_Summary.pdf CDC – http://www.cdc.gov/hiv/topics/testing/index.htm