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Discordant Serology and Nucleic Acid Testing Results for HIV, HBV and HCV in 2010

Analysis of 2010 data on Nucleic Acid Testing (NAT) and serology results for HIV, HBV, and HCV among organ donors. Comparison reveals insights into donor screening effectiveness and infection detection rates.

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Discordant Serology and Nucleic Acid Testing Results for HIV, HBV and HCV in 2010

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  1. Discordant Serology and Nucleic Acid Testing Results for HIV, HBV and HCV in 2010 Nicole Theodoropoulos1,3, Marek Nowicki4, Claudia Chinchilla-Reyes4, Carol Pancoska5, Andres Jaramillo6, Tom Mone7, Rick Hasz8, Martin D. Jendrisak6, Daniela P Ladner2,3, Michael G Ison1-3 1Divisions of Infectious Diseases and 2Organ Transplantation, 3Northwestern University Transplant Outcomes Research Collaborative, Northwestern University, 4Mendez National Institute of Transplantation, 5Labs Inc, 6Gift of Hope Organ & Tissue Donor Network, 7OneLegacy, 8Gift of Life Donor Program American Transplant Congress – Boston, Massachusetts June 3, 2012

  2. Disclosures • I have no financial relationships to disclose within the past 12 months relevant to my presentation. • I do not intend to reference unlabeled/unapproved uses of drugs or products in my presentation.

  3. Background: Significant Organ Shortage *Waiting list deaths includes removals for death, too sick to transplant, and those non-transplanted removals identified to have died within seven days of removal from linkage to SSDMF data. Based on OPTN data as of April 16, 2010. http://optn.transplant.hrsa.gov/

  4. Background: Donor Screening Policy • OPTN Policy 2.2: Donor Evaluation • Requires OPO to: • Obtain a medical & social history of the donor • Review the donor’s chart • Perform a physical examination of the donor • Perform FDA licensed, approved, or cleared screening tests • Serology for: HIV, HCV, HBsAg, HBcAb, CMV, EBV, and syphilis • Additional testing may be done at the discretion of the OPO or accepting transplant center • OPTN Policy 4.1: Screening Donors for HIV • Prohibits the use of donors with + HIV test result • Defines a donor at “increased risk of HIV, HBV or HCV transmission” • OPO must inform transplant center if the donor is increased risk • Transplant Center must obtain special consent from the recipient to use organs from an increased risk donor http://optn.transplant.hrsa.gov/policiesAndBylaws/policies.asp Rogerset al.MMWR. 1994;43(RR-8):1-17.

  5. Background: Nucleic Acid Testing (NAT) • NAT can detect recent infection • NAT increasingly used for donor screening3,4 Window Periods by assay type1,2 1Kucirka L et al. Am J Transplant 2011;11(6):1188-200. 2Kucirka L et al. Am J Transplant 2011;11(6):1176-87. 3Orlowski et al. Am J Transplant. 2009; 9: 555. 4Thedoropoulos N et al. Abstract LB17. ATC 2012.

  6. Background: Nucleic Acid Testing (NAT) • Recent Consensus Conference reviewed issues related to use of NAT for donor screening1 • Estimated the impact of false positive testing • Recommended NAT screening of increased risk donors and those with inadequate risk information only 1Humar et al. Am J Transplant. 2010; 10: 889-899.

  7. Study Objectives • To quantify the number of additional infections detected when NAT is added to routine serologic screening • To attempt to quantify non-reproducibly positive NAT rates

  8. Methods: Sites & Serologic Screening Screening data on all potential deceased organ donors was obtained from 3 US OPO-affiliated laboratories in 2010, representing: • 15 Organ Procurement Organizations • ~35% of the US Donor Pool All potential deceased organ donors were screened for HIV, HBV, and HCV according to current OPTN Policy • Genetic Systems HIV-1/HIV-2 plus O EIA (Bio-Rad Laboratories) • Genetic Systems HBsAg EIA 3.0 (Bio-Rad Laboratories) • ORTHO HBc ELISA Test System (Ortho-Clinical Diagnostics, Inc.) • ORTHO HCV Version 3.0 ELISA Test System (Ortho-Clinical Diagnostics, Inc.) • All assays performed according to the package insert

  9. Methods: NAT Screening • Polymerase Chain Reaction (PCR) Assays • COBAS Ampliscreen HIV-1 Test Version 1.5, Roche Molecular Systems • COBAS Ampliscreen HCV Test Version 2.0, Roche Molecular Systems • COBAS HBV Ampliscreen, Roche Molecular systems* • Transcription-Mediated Amplification (TMA) Assay • Procleix HIV-1/HCV Assay, Gen-Probe, Inc. *HBV NAT performed for all PDOD from 4/5 client OPOs

  10. Results: Serologic Screening • 22 donors positive for both HBsAg and HBcAb.

  11. Results: NAT Screening Total NAT Screening Volumes by Lab

  12. Results: HIV NAT Screening

  13. Results: HIV NAT Non-Reproducible Results • 10 HIV seronegative donors with + NAT • One PCR-based lab • 2/10 NAT were repeated and were found to be non-reproducibly positive (NRP) • The lab performed an extensive quality investigation • Examination of the equipment and lab by the assay manufacturer • Re-training of lab technicians • Technician monitoring • Machine sterilization • No definite root cause was determined • Lab changed to a TMA NAT platform • Lab C used TMA for NAT • Built-in confirmatory step • All initial NAT + results were confirmed by discriminatory assay

  14. Results: HBV NAT Screening • *4 isolated +HBcAb; 4 +HBsAg and +HBcAb • °56/60 were isolated +HBcAb

  15. Results: HCV NAT Screening

  16. Conclusions • NAT was positive in 15 (0.4%) seronegative donors • All HIV antibody negative/NAT positive results resulted from one PCR-based lab • 20% were shown to be non-reproducibly positive • Built-in confirmatory step in the TMA NAT may account for fewer NRP results seen with this assay1 • Rapid and robust quality assurance is key • 1.8% PODs screened were HCV Ab+/NAT – • 12% PODs screened were HBV Ab+/NAT – • HBV Ab + and HCV Ab+ donors have variable utilization2,3 • The use of NAT screening could improve utilization of HBV Ab + and HCV Ab + donor organs 1 Chinchilla-Reyes C et al. Abstract 387. ATC 2012. 2Kucirka LM et al. Am J Transplant 2010 May;10(5):1238-46. 3Taylor RM et al. Transplant Proc 2010;42:4479-87.

  17. Future Directions • We intend to ask OPOs to share their primary donor screening data • We plan to link this data with OPTN donor data to determine • The true incidence of seronegative, NAT positive donors • The effect of NAT screening on organ utilization • The false positive rates of NAT in the deceased organ donor population • The effect of the type of NAT assay (PCR vs TMA) on false positive results • All donor screening results should be collected in a national database

  18. Questions? Nicole Theodoropoulos, MD 312-695-5054 n-theodoropoulos@md.northwestern.edu nicoletheo15@gmail.com

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