Trofile Assay Access Program

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Trofile Assay Access Program

• Virginia Department of Health
• Division of Disease Prevention
• AIDS Drug Assistance Program (ADAP)
• 2008

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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

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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.

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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.

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What about insured clients?

• Clients with Medicare, Medicaid, or private
  insurance must use that coverage to obtain a
  Trofile test.

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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).

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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)

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Trofile Assay Access contd

• 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

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Trofile Assay Access Collection Sites

• List of currently approved laboratory collection
  sites found on ADAP website at
• http//www.vdh.virginia.gov/epidemiology/DiseasePr
  evention/Programs/ADAP/support.htm
• List will be updated as new collection sites come
  on board.

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maraviroc (Selzentry) Info How It Works

• Maraviroc (Selzentry)-manufactured currently by
  Pfizer
• Entry-inhibitor
• CCR5 antagonist only
• Blocks the CCR5 chemokine receptor on the
  clients CD4 T cell to prevent entry of the R5
  tropic HIV-1 virus.
• maraviroc not effective if clients virus is X4
  tropic or Dual/Mixed (D/M) tropic.

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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 Exception Form
  required only with the initial prescription.

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maraviroc Exception Criteria contd

• 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.

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Tropism Defined
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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 clients
  virus uses to enter the CD4 T cell (aka the
  helper cell.)

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Tropism contd

• 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.

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What is the Trofile Assay?
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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 clients tropism
  before approving for maraviroc usage
• MUST be performed if clinician is considering use
  of maraviroc in clients HAART/ART

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Trofile Assay description

• Clients 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 clients envelope
  protein contained in the clients 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.

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Trofile Assay description contd

• 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 identifies
  which tropism the virus exhibits.

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Trofile assay description contd

• 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

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Trofile Assay Access Program Description
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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

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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.

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Medical Provider Responsibilities
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Medical Provider Responsibilities

• Medical Provider
• Determines if client appears to meet maraviroc
  exception criteria
• Either contacts VDH Lab Liaison at [phone]
  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 [phone]

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Medical Provider Responsibilities contd

• Medical Provider upon receipt of approval from
  VDH Lab Liaison
• Contacts Laboratory collection site to set up
  clients 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

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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

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VDH Lab Liaison Responsibilities contd

• 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.

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VDH Lab Liaison Responsibilities contd

• 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

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Monogram Biosciences Responsibilities
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Monograms 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 clients 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

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Laboratory/Collection Site Responsibilities
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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

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Lab/Collection Site Responsibilities contd

• 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

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Test Result Reporting Final Processing
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Test Result Reporting Final processing contd

• 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

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Test Result Reporting Final Processing contd

• Medical Provider will
• Issue prescription for maraviroc (Selzentry)
• Local Health Dept. ADAP Coordinator will
• Process approval proceed with localitys usual
  procedure for filling ADAP prescriptions if
  patient approved for maraviroc usage

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VDH ADAP Trofile Website Info

• VDH ADAP Website
• http//www.vdh.virginia.gov/epidemiology/DiseasePr
  evention/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

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Contact Info for VDH ADAP Trofile Program

• VDH Laboratory Liaison
• Phyllis Morris, [phone]
• Phyllis.Morris_at_vdh.virginia.gov
• VDH ADAP Coordinator
• Rachel Rees, [phone]
• Rachel.Rees_at_vdh.virginia.gov

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Additional Resource Info

• Trofile Assay Info
• http//www.trofileassay.com
• maraviroc(Selzentry) Info
• http//www.fda.gov/bbs/topics/news/2007/new01677.h
  tml

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Questions?

• Please contact Phyllis Morris, VDH Lab Liaison,
  at [phone] or via Phyllis.Morris_at_vdh.virgin
  ia.gov

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