National HIV Drug Interaction and Antiretroviral (ARV) Therapeutic by rub18840

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									               National HIV Drug Interaction and Antiretroviral (ARV) Therapeutic Drug Monitoring (TDM) Registry
                                              N Higgins1, J Slish1, L Catanzaro1, NS Boston1, R DiFrancesco1, CB Hsiao2, A Sulaiman2 , G Morse1,                                                                                                                                                                                                      Abstract RP353
                                                                                            1University    at Buffalo School of Pharmacy and Pharmaceutical Sciences;
                                                                                                            2Erie County Medical Center, Buffalo, New York




                           ABSTRACT                                                               SITE LOCATIONS                                 TDM REGISTRY PROCESS                                                                                                                       RESULTS
Objective: Therapeutic drug monitoring (TDM) of antiretroviral
(ARV) agents is an area of growing involvement for pharmacists.                                                                             HIV Drug Interactions and Antiretroviral TDM                                                                  Sex (n=464)
                                                                                                                                                                                                                                                                                                                                                                Race (n=464)


Based on a model adherence-pharmacology program within our                                                                                                    Registry
                                                                                                                                                                                                                                                                                                                                           7%              3%
                                                                                                                                                                                                                                                     2%

HIV clinic, a nationwide TDM research program has been                                                                                                                                                                      30%
                                                                                                                                                                                                                                                                                                                               12%
                                                                                                                                                                                                                                                                                                                                                                                        36%


implemented using web-based networking for regional HIV clinics.                                                                                                                                                                                                                                                                                                                                Caucasian
                                                                                                                                                                                                                                                                                                                                                                                                Black
                                                                                                                                                                                                                                                                                                           Males
Patient samples are collected and shipped to a central lab for real-                                                                                   Site Registers on HIV                                                                                                                               Females
                                                                                                                                                                                                                                                                                                           Unknown
                                                                                                                                                                                                                                                                                                                                                                                                Hispanic
                                                                                                                                                                                                                                                                                                                                                                                                Other



time assay accompanied by a pharmacologic evaluation. The                                                                                            Pharmacotherapy Network                                                                                                                                                                                                                    Unknown



                                                                                                                                                       (www.hiv.buffalo.edu)
purpose of this study is to evaluate assay submissions within the                                                                                                                                                                                                               68%
                                                                                                                                                                                                                                                                                                                                     42%



registry to determine the reasons for TDM sampling and the ability                                                                                                                                  Later Goals:
                                                                                                                                                                                                   Pharmacogenomic
to provide pharmacologic interpretations of the samples.                                                                                            Sites obtain informed consent                    s        Viral
                                                                             Model Sites
                                                                             Nested Initiatives
                                                                                                                                                         and registers subject                         genetics
                                                                                                                                                                                                                                                Reason for Sampling (n=507)
                                                                                                                                                                                                                                                                                                                                                Pharmacologic Interpretations (n=425)
Methods: The University at Buffalo Laboratory for Antiviral
Research (UBLAR) has developed and validated a multiple analyte                                                                                                                                                       160


                                                                                                                                                                                                                      140
                                                                                                                                                                                                                                                                                                                         200


assay to measure protease inhibitor and non-nucleoside reverse                                                                                        Lab sends kit to site, site                                     120
                                                                                                                                                                                                                                                                              Decreased Liver Function
                                                                                                                                                                                                                                                                                                                         180

                                                                                                                                                                                                                                                                                                                         160
                                                                                                                                                      returns sample for assay
transcriptase inhibitor plasma concentrations. A web-based                                                                                                                                                            100
                                                                                                                                                                                                                                                                              Suspected Food Interaction/Malabsorption
                                                                                                                                                                                                                                                                              Suspected Toxicity
                                                                                                                                                                                                                                                                              Suspected Drug Interaction
                                                                                                                                                                                                                                                                                                                         140

                                                                                                                                                                                                                                                                                                                         120
                                                                                                                                                                                                                                                                                                                                                                                              Not Available
                                                                                                                                                                                                                                                                                                                                                                                              High
                                                                                                                                                                                                                      80

database facilitates the collection of plasma samples and their                                      METHODS                                                                                                          60
                                                                                                                                                                                                                                                                              Virologic Failure
                                                                                                                                                                                                                                                                              Suspected Non-Adherence
                                                                                                                                                                                                                                                                              Other/Unspecified
                                                                                                                                                                                                                                                                                                                         100

                                                                                                                                                                                                                                                                                                                         80
                                                                                                                                                                                                                                                                                                                                                                                              Not Interpretable
                                                                                                                                                                                                                                                                                                                                                                                              Low
                                                                                                                                                                                                                                                                                                                                                                                              Within

shipment to the UBLAR. Sites must obtain IRB approval and                                                                                                                                                             40                                                                                                 60


                                                                                                                                                     Lab provides assay result                                        20                                                                                                 40

informed consent, collect, store and ship blood samples according                                                                                     and interpretation of PK
                                                                                                                                                                                                                                                                                                                         20


                                                                       •   The University at Buffalo Laboratory for Antiviral
                                                                                                                                                                                                                       0
                                                                                                                                                                                                                                    Reason for Sampling                                                                   0

to the registry protocol. A reporting mechanism provides the                                                                                                   result
                                                                                                                                                                                                                                                                                                                                                Pharmacologic Interpretation

                                                                           Research (UBLAR) measures PI and NNRTI plasma
participating sites with assay results and a pharmacologic                 concentrations
interpretation. A retrospective analysis will be performed to          •   A web-based database facilitates the collection of
evaluate site registration, reason for TDM sampling, and the ability       plasma samples and their shipment to the UBLAR                              Database for Population
                                                                                                                                                             Analyses                                                                                                         CONCLUSIONS
to provide pharmacologic interpretations between 12/01/2001 and        •   Sites must obtain IRB approval and informed consent,
9/22/2005 on the samples submitted.                                        collect, store and ship blood samples according to the
                                                                           registry protocol                                                                                                                                 •    A national TDM registry has been successfully
                         BACKGROUND                                    •   A reporting mechanism provides the participating sites            TROUGH CONCENTRATIONS*                                                               implemented with site registration, data entry and ARV
                                                                           with assay results and a pharmacologic interpretation                                                                                                  assay mechanisms are well-integrated
•    PIs and NNRTIS are used at fixed doses                            •   A retrospective analysis was performed to evaluate site     Antiretroviral                      Target Trough                                     •    Complex ARV regimens are prescribed with TDM utilized
•    Inter- and intra-patient variability in absorption provide the        registration, reason for TDM sampling, and the ability to                                                                                              to help manage drug resistance, drug-drug, or drug-
                                                                           provide pharmacologic interpretations between                                                   Range
     rationale for therapeutic drug monitoring (TDM)                                                                                                                                                                              disease state interactions
                                                                           12/01/2001 and 9/22/2005 on the samples submitted           Atazanavir (ATV)                    150-1000ng/ml
•    Suboptimal concentrations lead to virologic failure and                                                                                                                                                                 •    Pharmacologic interpretations were able to be provided
     development of resistance                                                                                                                                                                                                    for the majority of TDM samples
•    Elevated concentrations are associated with toxicities                                 INCLUSION CRITERIA                         Amprenavir (APV)                    400-2200ng/ml                                     •    Population ARV pharmacokinetic models are being
•    Potential for multiple drug-drug interactions                                                                                                                                                                                developed to enable pharmacologic interpretation to be
•    Hepatic disease may result in unpredictable concentrations                                                                        Indinavir (IDV)                     100-1000ng/ml                                          provided when samples are not obtained at desired
•    Patient specific factors such as achlorhydria, drug-food          • Patient is receiving PI or NNRTI                                                                                                                         trough sampling times
     interactions, or diarrhea can result in malabsorption             • On the same ARV regimen for >14 days prior to study
•    A nationwide TDM research program has been implemented              entry                                                         Lopinavir/ritonavir                 1000-9000ng/ml
     based on a model adherence-pharmacology program within            • Patients ≥ 18 years of age, either sex                        (LPVr)                                                                                     DISCLOSURE:
     our HIV clinic                                                    • Ability to provide written informed consent                                                                                                              The authors have the following to disclose:
                                                                       • And one or more of the following:                             Nelfinavir (NFV) (M8)               800-3000ng/ml                                          Niamh Higgins - nothing to disclose
                                                                                                                                                                                                                                  Gene D. Morse - nothing to disclose
                                                                          – Suspected drug interaction                                 Saquinavir (SQV)                    250-600ng/ml                                           Judianne Slish – speakers’ bureau: Pfizer
                          OBJECTIVES                                      – Suspected malabsorption/food interaction                                                                                                              Linda Catanzaro – speakers’ bureau: Gilead
                                                                          – Liver dysfunction (e.g. HCV, HBV)                          Efavirenz (EFV)                     1000-4000ng/ml                                         Naomi Boston - nothing to disclose
 •   The purpose of this study is to evaluate assay submissions           – Virologic Failure                                                                                                                                     Robin DiFrancesco - nothing to disclose
                                                                                                                                                                                                                                  Chiu-Bin Hsiao –research grants: Eli Lilly, Pfizer, Bristol-Myers
     within the registry to determine the reasons for TDM                 – Suspected ARV toxicity                                     *Trough concentrations of PIs and NNRTIs are evaluated
                                                                                                                                                                                                                                  Squibb, Wyatt; speakers’ bureau: Bristol-Myers Squibb, Cubist, Wyatt
     sampling and the ability to provide pharmacologic                                                                                 Troughs are analyzed by High Performance Liquid Chromatography
                                                                          – Suspected Non-Adherence                                        (HPLC)                                                                                 Adel Sulaiman - nothing to disclose
     interpretations of the samples

								
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