Trofile Assay Access Program

1. Trofile Assay Access Program Virginia Department of Health Division of Disease Prevention AIDS Drug Assistance Program (ADAP) 2008

2. Presentation Overview • Trofile Program Purpose • Client Eligibility Info • Trofile & maraviroc (Selzentry) Exception Criteria • 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 that exhibits virologic failure (i.e., treatment experienced) and 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 • “Nucleoside/Nucleotide Reverse Transcriptase Inhibitor (NRTI) and Non-Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NNRTI) experienced or contraindicated with a viral load greater than 1,000 copies/ml, and prior experience with one or more Protease Inhibitors (PIs).”

7. Trofile Assay Access • Access to designated laboratory collection sites • Will begin with certain, designated VDH local health department sites properly equipped & staffed for collection • Currently starting with: • Peninsula Health District (Newport News Main) • Roanoke City Health District (Main location only) • Western Tidewater Health District (all four sites including Suffolk, Franklin, Southampton, and Isle of Wight)

8. Trofile Assay Access cont’d: • Expansion plans include: • Currently negotiating with designated commercial reference laboratory collection sites • Currently negotiating with designated independent laboratory collection sites • Plan to expand to other local health districts

9. 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.

10. 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.

11. maraviroc (Selzentry) Exception Criteria • “NRTI and NNRTI experienced, or contraindicated, and prior experience with one (1) or more PIs, with 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.

12. maraviroc Exception Criteria cont’d: • Note: The exception will be approved if a 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.

13. Tropism Defined

14. 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.”)

15. 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.

16. What is the Trofile Assay?

17. What is the Trofile Assay? • Currently, sole provider for assay: Monogram Biosciences, Inc. (South San Francisco, California) • 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 in client’s HAART/ART

18. 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.

19. 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.

20. 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

21. Trofile Assay Access Program Description

22. 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

23. 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.

24. Medical Provider Responsibilities

25. 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

26. 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 • Upon receipt of two part Monogram Biosciences Test Request form from Monogram, will complete all sections of 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

27. 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

28. 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.

29. 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 • 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

30. Monogram Biosciences Responsibilities

31. 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 local health department or independent lab collection site to be used) • 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

32. Laboratory/Collection Site Responsibilities

33. 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

34. Lab/Collection Site Responsibilities cont’d • 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

35. Test Result Reporting & Final Processing

36. 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

37. 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

38. 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

39. 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

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

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

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