Trofile Assay Access Program

1. Trofile Assay Access Program Virginia Department of Health Division of Disease Prevention AIDS Drug Assistance Program (ADAP) Revised January 2010

2. Presentation Overview • Trofile Program Purpose • Client Eligibility Info • Trofile & maraviroc (Selzentry) Exception Criteria-Revised December 2009 • Trofile Assay Info • Trofile Assay Access Program Description & Definition of Duties • Contact & Resource Info

3. Purpose of Trofile Assay Access Program • Provides access for all uninsured ADAP clients to receive tropism testing via the Monogram Biosciences Trofile assay if the medical provider deems such testing necessary. • Tropism testing is an allowable expenditure under Ryan White Part B funding under medical care/lab services.

4. What clients are eligible? • Any uninsured ADAP client (treatment experienced) where the medical provider is considering use of the CCR5 antagonist medication maraviroc (Selzentry). • If maraviroc is being considered, client MUST have a tropism test performed and demonstrate a positive result (R5 tropism) before being approved for maraviroc usage.

5. What about insured clients? • Clients with Medicare, Medicaid, or private insurance must use that coverage to obtain a Trofile test.

6. Trofile Exception Criteria • Clients must exhibit “a viral load greater than 1,000 copies/ml. For maximum accuracy, the viral load should be drawn within two to four (2-4) weeks of the Trofile assay draw.”

7. Trofile Assay Access • Access to designated laboratory collection sites • Began with certain, designated VDH local health department sites properly equipped & staffed for collection • Currently have sample collection MOAs with: • Peninsula Health Department (Newport News)-until 4/1/2010 • Roanoke City Health Department (Main location) • May utilize any of the 45 LabCorp Patient Service Center locations (PSCs) after completion of VDH pre-authorization phase

8. Labcorp Option • Monogram Biosciences became a subsidiary of Labcorp in August 2009 • Additional option available for VDH local health departments to use regarding Trofile sample collection

9. LabCorp Access Option • Labcorp Access Option • Two choices for VDH Local Health Departments once pre-authorization steps completed: • Collect @ HD if HD has -20C freezer & have Labcorp retrieve, or • Process all required paperwork & schedule client to go to Labcorp Patient Service Center (PSC) for Trofile sample collection. • Reminder: Ensure Labcorp Test Requisition contains Trofile Test Code 829574 & record “Bill VDH ADAP” in comments in billing section of form

10. LabCorp Option (cont’d) • Reminders for Labcorp Option: • Schedule venipunctures with Labcorp PSCs only on Monday-Wednesday (no Thursday or Friday draws due to delivery issues to Monogram) • Do not schedule venipunctures during these four holiday weeks: July 4th, Thanksgiving, Christmas, or New Year’s • Ensure the client has the fully completed Monogram Test Request Form, signed client consent form copy & the Labcorp requisition form to take to Labcorp

11. Trofile Assay Access Collection Sites: • List of currently approved laboratory collection sites found on ADAP website at: • http://www.vdh.virginia.gov/epidemiology/DiseasePrevention/Programs/ADAP/support.htm • List will be updated as new collection sites come on board.

12. maraviroc (Selzentry) Info & How It Works • Maraviroc (Selzentry)-manufactured currently by Pfizer • Entry-inhibitor • CCR5 antagonist only: • Blocks the CCR5 chemokine receptor on the client’s CD4+ T cell to prevent entry of the R5 tropic HIV-1 virus. • maraviroc not effective if client’s virus is X4 tropic or Dual/Mixed (D/M) tropic.

13. maraviroc (Selzentry) Exception Criteria • “NRTI and NNRTI experienced or contraindicated and prior experience with 1 or more PIs, or raltegravir, OR intolerance to current regimen AND • A positive blood test for the CCR5 co-receptor test (Trofile) within three (3) months.” • ADAP Medication/Lab ExceptionForm required only with the initial prescription.

14. maraviroc Exception Criteria cont’d: • Note: The exception will be approved for a treatment experienced client if the client has been taking a regimen that included this medication prior to ADAP enrollment, or accessing the medication through clinical trial or expanded access. This may be documented on the VDH ADAP Medication/Lab Exception Form under “Reason for Exception” section.

15. Tropism Defined

16. What is Tropism? • Tropism refers to the “affinity” of a virus, or the preferred pathway a virus uses to enter a certain cell type. • Specifically for the HIV-1 virus, the type of tropism refers to which co-receptor the client’s virus uses to enter the CD4+ T cell (aka the “helper cell.”)

17. Tropism cont’d • HIV-1 viruses currently exhibit one of four tropism classifications: • R5: Uses CCR5 co-receptor only • X4: Uses CXCR4 co-receptor only • Dual-tropic (D): Uses either the CCR5 or CXCR4 co-receptor • Mixed-tropic (M): HIV-1 virus may be mosaic, wild-type, etc., that may contain combinations of R5, X4, and/or dual tropic viruses; uses either R5 or X4 co-receptor or both co-receptors.

18. What is the Trofile Assay?

19. What is the Trofile Assay? • Currently, sole provider for assay: Monogram Biosciences, Inc. (South San Francisco, California), a subsidiary of LabCorp as of August 2009 • Currently the only CLIA-validated tropism assay available for use to determine client’s tropism before approving for maraviroc usage • MUST be performed if clinician is considering use of maraviroc (or in the future, any R5 antagonist) in client’s HAART/ART

20. Trofile Assay description • Client’s sample containing at least 1000 copies/ml or more of the HIV-1 virus is amplified (via PCR) to generate sufficient copies of the gp160 coding region of the client’s envelope protein contained in the client’s HIV-1 virus. • The amplified copies are introduced into a CCR5 “expressing” cell line, and into a CXCR4 “expressing” cell line, resulting in two “infected” cell lines. • After “incubation” to allow the viral particles to infect the cell lines, a single round of viral replication occurs.

21. Trofile Assay description cont’d: • The “infected” cell lines post viral replication are tested in the presence and absence of an antagonist (maraviroc). • A reporter gene then expresses its light-emitting indicator gene (luciferase), which emits a visible signal (fluorescence), that identifieswhich tropism the virus exhibits.

22. Trofile assay description cont’d: • Results are visualized/expressed as follows: • R5 Trophotype (tropism) • Fluoresces only with the CCR5 cell line in the absence of the antagonist drug (maraviroc) • X4 Trophotype (tropism) • Fluoresces only with the CXCR4 cell in the absence of the antagonist • D/M (dual/mixed) Trophotype (tropism) • Fluoresces in both the CCR5 and CXCR4 cell lines in the absence of the antagonist

23. Trofile Assay Access Program Description

24. Trofile Assay Access Program Description • Provider determination of need for maraviroc usage • VDH review process & approval/denial for Trofile draw • Scheduling of venipuncture • Laboratory collection & initial processing • Courier retrieval of frozen sample • Result reporting & approval/denial for maraviroc usage • Filling of ADAP prescription • Reimbursement to collection sites (for sites with an MOA with VDH); or processing of Monogram invoice if direct billed from Monogram

25. Special Considerations Involved • Specialized laboratory test collection procedures involved • Sample must be collected in PPT tubes • Sample must be centrifuged and frozen at -20C within two (2) hours of collection • Collection sites must be properly staffed and equipped to handle specimen collection • Viral load integrity must be maintained, and must be greater than or equal to 1000 copies/ml • Most recent viral load must have been measured within 2-4 weeks before Trofile venipuncture collection date.

26. Medical Provider Responsibilities

27. Medical Provider Responsibilities: • Medical Provider: • Determines if client appears to meet maraviroc exception criteria • Either contacts VDH Lab Liaison at (804) 864-8000 or downloads the following from the ADAP website: • ADAP Medication/Lab Exception Form • Client Consent Form • List of VDH contracted lab/collection sites • Completes ADAP Medication/Lab Exception Form & signed consent form & faxes both to VDH Lab Liaison at (804) 864-8050

28. Medical Provider Responsibilities cont’d • Medical Provider upon receipt of approval from VDH Lab Liaison: • Contacts Laboratory collection site to set up client’s venipuncture appointment • Will complete all sections of Monogram Biosciences Trofile test request form except for date/time collected & date/time separated. • Will send two part test request form & signed client consent form with client to take to lab collection site • Will retain a photocopy of both the test request form & the signed client consent form for office records

29. VDH Lab Liaison Responsibilities: • Conducts VDH ADAP Trofile Review Process to determine if client meets Trofile assay eligibility criteria • Lab Liaison will: • Review completed ADAP Medication/Lab Exception Form; contact medical provider for any missing info • Verify ADAP enrollment; if not enrolled or eligibility re-determination due, will contact medical provider to send client to local health department to complete enrollment or re-determine eligibility

30. VDH Lab Liaison Responsibilities cont’d: • Contact medical provider for identity of provider-selected laboratory collection site • Complete applicable sections of VDH Test Authorization Form & forward to Assistant Director of HIV Care Services for approval.

31. VDH Lab Liaison Responsibilities cont’d: • Fax completed/approved Test Authorization Form to Monogram Biosciences • Confirm mailing address/contact info for Monogram to send test request form to medical provider if needed • Confirm shipping address/contact info for Monogram to send PPT tubes to lab collection site if local health department or independent lab collection site to be used & site does not already have PPT tubes on hand. If using Labcorp PSC, Labcorp already has tubes on hand.

32. Monogram Biosciences Responsibilities

33. Monogram’s Responsibilities: • Monogram Biosciences: • Upon receipt of approved test authorization, sends test request form to medical provider and two PPT tubes to lab collection site (if needed) • Will dispatch courier service to retrieve & package client’s frozen sample tubes post venipuncture when notified by lab collection site • Provides test result report to VDH ADAP program and to medical provider within 14 days of sample receipt • Bills VDH ADAP program for completed Trofile test that yields an actual tropism result

34. Laboratory/Collection Site Responsibilities

35. Laboratory/Collection Site Responsibilities • Laboratory/Collection Site will: • Document scheduled venipuncture appointment • Perform venipuncture & initial processing services to include checking form completeness, sample collection, centrifugation, freezing, and storage of back copy of test request form and client consent form • Will contact Monogram Biosciences for courier service to be dispatched to retrieve frozen sample

36. Lab/Collection Site Responsibilities cont’d • If Peninsula or Roanoke City HD, will complete ATV form if local health department site or submit purchase order (for other sites) on monthly basis & submit to VDH Lab Liaison for processing for reimbursement of specimen collection/processing fee • Will fax copy of airbill & client consent form to VDH Lab Liaison • Will assist courier with initial packaging of frozen samples & ensure compliance with IATA shipping guidelines

37. Test Result Reporting & Final Processing

38. Test Result Reporting & Final processing cont’d: • Upon receipt of final test report: • Lab Liaison will: • Document on ADAP Medication/Lab Exception Form approval/denial of maraviroc use • Will notify local health department ADAP Coordinator by phone and fax of approval/denial of maraviroc use via Medication Exception Form • Will notify medical provider of approval of maraviroc use & to issue prescription request

39. Test Result Reporting & Final Processing cont’d: • Medical Provider will: • Issue prescription for maraviroc (Selzentry) • Local Health Dept. ADAP Coordinator will: • Process approval & proceed with locality’s usual procedure for filling ADAP prescriptions if patient approved for maraviroc usage

40. VDH ADAP Trofile Website Info • VDH ADAP Website: • http://www.vdh.virginia.gov/epidemiology/DiseasePrevention/Programs/ADAP/support.htm • Contains the following info: • VDH ADAP Medication/Lab Exception Form • VDH/Monogram Biosciences Client Consent & Release of Information Form • List of VDH contracted laboratory/collection sites • Frequently Asked Questions Info • Links to additional resource information • Copy of this Power Point presentation

41. Contact Info for VDH ADAP Trofile Program • VDH Laboratory Liaison • Phyllis Morris, (804) 864-8000 • Phyllis.Morris@vdh.virginia.gov • VDH ADAP Coordinator • Rachel Rees, (804) 864-7919 • Rachel.Rees@vdh.virginia.gov

42. Additional Resource Info • Trofile Assay Info: • http://www.trofileassay.com • maraviroc(Selzentry) Info: • http://www.fda.gov/bbs/topics/news/2007/new01677.html

43. Questions? • Please contact Phyllis Morris, VDH Lab Liaison, at (804) 864-8000 or via Phyllis.Morris@vdh.virginia.gov

44. Thank you for your time in reviewing this presentation, and please feel free to contact us with suggested improvements.