Investigation of the Increased Rate of False Positive

Investigation of the Increased Rate of False Positive Results Using an Oral Mucosal Rapid HIV Test Centers for Disease Control and Prevention Minnesota Department of Health New Jersey Department of Health & Senior Services Wisconsin Division of Public Health

Background • University of Minnesota demonstration project • Finger stick and oral mucosal transudate (OMT) rapid HIV tests • Incidence of Type I, II discordant results • Factors associated with discordant results • OMT test Clinical Laboratory Improvement Amendment (CLIA) waived • OMT test was scheduled for launch end- August 2004

Preliminary Data • July 2002 – April 14, 2004: – 2, 022 individuals tested – 7 OMT false positives (0. 35%) • April 15, 2004 – July 22, 2004: – 266 individuals tested – 15 OMT false positives (5. 6%) • 5 -20% false positive rates reported in community trials

Investigation • Started with Epi Aid investigation on invitation of Minnesota Department of Health • Developed into multi-state investigation • Key component is case control study

Objectives • • Determine rate of false positive OMT rapid HIV tests Determine factors associated with false positive OMT tests • • • Host immunological factors Medical conditions Interfering substances

Sites and Duration • New Jersey, Wisconsin, Minnesota • New Jersey: – – – Robert Wood Johnson (New Brunswick) Henry J. Austin (Trenton) NJCRI Bergen County Atlantic City Health Department East Orange Health Department • 4 months

Study Population • Cases (n=150): • • 50 to be enrolled in NJ Reactive OMT rapid test Non-reactive finger-stick rapid test Exclude HIV positive individuals after confirmatory HIV test result • Controls (n=450): • • 150 to be enrolled in NJ Non-reactive OMT rapid test Non-reactive finger-stick rapid test Exclude HIV positive individuals after confirmatory HIV test result • Exclude temporally related controls after case confirmed to be HIV positive

Eligibility Criteria • • 18 yrs or older No previous HIV diagnosis No history of antiretroviral therapy No HIV vaccine

Methods • Phase I • • Conduct fingerstick and OMT rapid HIV tests Administer questionnaire Collect serum and OMT specimens Perform HIV confirmatory testing on serum and OMT Analyze test devices Bank specimens for Phase II If sufficient OMT false positives, continue study

Methods • Phase II • • Continue recruitment of cases and controls Perform all other laboratory tests Analyze data using multivariate logistic regression Continue device analysis

Laboratory Tests – Serum: – – – – – Hepatitis A, B, C Rheumatoid factor EBV Quantitative HCG pregnancy test ANA RPR Protein electrophoresis Gel electrophoresis with immunofixation for Ig estimation HSV I and II CMV – Oral fluid: – Confirmatory HIV EIA/WB – Immunoglobulin estimation- protein electrophoresis

Analysis of Test Devices • Microscopy or other physical methods to characterize false positive results • Ship devices to CDC

Step 1: Enrolling Study Participants

Enrolling a Case 1. Administer written consent for rapid tests (stage 1) 2. Perform fingerstick and OMT rapid tests 3. Assess if potential case • • 4. 5. 6. 7. 8. Non-reactive fingerstick result Reactive OMT result Check for eligibility Administer written consent (stage 2) Administer questionnaire Collect blood and OMT specimens Ship specimens and devices to CDC

Enrolling a Control 1. Administer written consent for rapid tests (stage 1) 2. Perform fingerstick and OMT rapid tests 3. Assess if potential control • • 4. 5. 6. 7. 8. Non-reactive fingerstick result Non-reactive OMT result Check for eligibility Administer written consent (stage 2) Administer questionnaire Collect blood and OMT specimens Ship specimens and devices to CDC

Clinic Flow Recruit CASE: Reactive OMT Non-reactive fingerstick Case Control # 1 Control # 2 Control # 3 Recruit next 3 consecutive CONTROLS: Non-reactive OMT Non-reactive fingerstick

Step 2: Interview

Questionnaire • Hand-held devices • Enter – subject ID, location, date and time – fingerstick and OMT device lot numbers – fingerstick and OMT test results • Go through all questions • Confirm subject ID at end of interview

Step 3: Shipping Specimens and Devices to CDC

Specimens and Devices • Specimens – 37 m. L venipuncture whole blood • 3 serum separator tubes: red top/tiger top (10 m. L each) • 1 plasma preparation tube (PPT) or lavender top EDTA (7 m. L) – OMT • 2 Orasure OMT • Devices – Rapid OMT and fingerstick for all cases and controls

Labels • Serum, plasma, OMT – Subject ID label – Gender and CDC lab project number label • Mp 225 • Fp 225 – Seal lid with adhesive tape: must be watertight – Wrap each vial/tube in foam envelope • Devices – Subject ID label – Place each OMT device in plastic ‘BIOHAZARD’ bag

Packaging Specimens • Plastic or metal containers – Follow all instructions included – Label container with name, address and phone number of shipper – Pad between vials with absorbent wrapping material – DO NOT place in this container

Specimen Submission Form • Appendix E in protocol • One copy between container and shipping box • Fax second copy to: – Dollene Hemmerlein – Krishna Jafa (770) 339 -5915 (404) 639 -8640

Outer packaging • Bio-transporter box – Follow all instructions included – Place copy of specimen submission form between container and box (fax second copy)

Label the Shipment – ALL labels on same side, alongside each other, clearly visible • • Name, address and phone number of shipper Diagnostic specimen UN 3373 label Orientation label (which side is ‘Up’) Address label: name, complete facility name, shipping address, phone number • Label with ‘Person Responsible for Shipment’ and 24 h/7 d phone number (no pagers)

Shipping Options • Preferred: – – Same day, on ice Serum: centrifuge, transfer into cryotubes Plasma: centrifuge, transfer into cryotubes, DO NOT freeze OMT • If centrifuge not available – – Same day, on ice Serum (in red top tube) Plasma (in lavender top tube), DO NOT freeze OMT • Ship all rapid test devices with specimens

Shipping • • • Fedex with CDC account number Typed or computer generated Sign form Monday through Thursday DO NOT ship on Friday Ms. Dollene Hemmerlein/Project 225 CDC Serum Bank 602 Webb Gin House Rd. Lawrenceville, Georgia 30045 Telephone: (770) 339 -5917

Supplies From CDC • Shipping containers and boxes • Labels: – Fedex – Gender, project number (e. g. Mp 225) • If required: – Cold packs – Tubes and vials

Summary • • Perform fingerstick and OMT rapid tests Recruit case and 3 consecutive controls Administer questionnaire Ship specimens and devices

Acknowledgments Division of HIV/AIDS Prevention, CDC Atlanta, GA Pragna Patel Patrick Sullivan Bernard Branson Kevin Delaney Duncan Mackellar Steven Ethridge Jeffrey Wiener Amy Drake Glenn Nakamura Tricia Hall Minnesota Department of Health Minneapolis, MN Stephen Swanson Tracy Sides Peter Carr Hennepin County Health Dept. Minneapolis, MN Deborah Persell Margaret Simpson New Jersey Department of Health and Senior Services Trenton, NJ Sindy M. Paul Rose Marie Martin Ken Earley Phil Brucolari Maureen Wolski Lorhetta Nichol Ayemaung Maung Rhonda Williams UMDNJ Robert Wood Johnson Medical School Eugene G. Martin Evan Cadoff Wisconsin Division of Public Health Madison, WI Alexandra Newman Jim Vergeront Kathleen Krchnavek Matt Maxwell Amy Doczy Mary Jo Hussey