1. HIV DiagnosticsandA New Testing Algorithm Lorna Seybolt, M.D., M.P.H. Louisiana State University Health Sciences Center Children’s Hospital New Orleans June 23, 2012

2. 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

3. 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

5. www.kff.org

6. FDA Timeline • 1985 • ELISA test kit for antibodies • 1987 • Western Blot • 1989 • Virus antigens (HIV-1)

7. 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

8. 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

9. FDA Timeline1996 • 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

10. FDA Timeline1996 • 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)

11. FDA Timeline • 1998 • WB for urine specimen testing • 1999 • Supplement to AMPLICOR HIV-1 Monitor • Extend LLQ from 400 50 copies/ml

12. FDA Timeline2001 • 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

13. FDA Timeline2002 • 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

14. ORA-What?

15. ORA-What? • 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

16. FDA Timeline2004 • 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

17. 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 • 3rd generation format

18. FDA TimelineMay 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

19. FDA Timeline2008 • March • VITROS Anti-HIV-1/2 (3rd gen) • Donor screening • December • COBAS TaqScreen MPX Test • First to detect HIV-2 and HIV-1 group O • Donated plasma

20. FDA Timeline • 2009 • Avioq HIV-1 Microelisa • Oral fluid, DBS • 2010 • Rapid INSTI HIV-1 60 sec antibody test • Abbott Architect 4th gen Ag/Ab Combo • 2011 • Bio-Rad GS HIV Ag/Ab Combo

21. Where Do Your Specimens Go?

22. What Happens When They Get There? ???

24. Generations?

25. Generations? • 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

31. Arch Intern Med. 2010;170(1):66-74

33. Who Is This Girl?AndWhy Is She Famous?

35. Available Tests • Conventional blood test • 1st, 2nd, 3rd, 4th generation EIA • Conventional oral fluid test • OraSure (collection device) • Avioq (used with specimens collected with OraSure device)

36. 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

37. Available Tests • Home tests • HomeAccess HIV-1 Test System

39. Available Tests • Urine test • Calypte ???

40. Available Tests • Urine test • Maxim HIV-1 Urine EIA • Cambridge Biotech Urine HIV-1 WB

41. Laboratory Based Tests

42. Bio-Rad GS HIV Combo Ag/Ab EIA20114th generation

43. Abbott Architect Ag/Ab Combo Assay20104th Generation

44. Avioq HIV-1 Microelisa20091st GenerationOral fluid, DBS, Serum, Plasma

45. VITROS HIV 1/220083rd Generation

46. ADVIA Centaur HIV 1/O/220063rd Generation

47. Rapid Test Kits

48. CDC

49. OraQuick Advance2002

50. Reveal G3