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unc-hiv-kidney-transplant-protocoldoc

By Charles Hernandez,2014-07-08 06:50
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unc-hiv-kidney-transplant-protocoldoc

    General HIV-Transplant Care Considerations

    Pretransplant

    ? Eligibility: patients must satisfy requirements prior to listing

    o Stable on ART x 6 months

    o CD4 > 200 x 6 months

    o HIV care provided at UNC

    o No active infections

    ? HIV evaluation

    o Patients will contact the ID clinic requesting an HIV-Transplant evaluation. They will be

    scheduled on a Tuesday or Thursday, and care will be supervised by a designated HIV

    physician (presently Drs. Quinlivan and Peppercorn and their fellows). If the patient is currently

    followed by the UNC ID clinic, they may continue care with their present physician or the

    designated HIV physicians.

    o An evaluation of the need to change ART will be made if:

    ? Regimen consists of a PI + NNRTI (due to unpredictable drug interactions)

    ? Regimen contains zidovudine or stavudine (due to potential for antagonism with MMF)

    o Pre-transplant PK/PD studies of ARVs or immunosuppressants will be considered

    o Any special prophylaxis requirements will be established, including TB

    o Patients will be assigned to an Enhanced Care nurse

    ? Nephrology evaluation

    o Follow current UNC renal transplant work-up with transplant surgery & nephrology

    o Patients to be notified of additional risks and possible difficulties of HIV+ transplantation

    Transplant Admission

    ? Transplant nephrology and the infectious diseases consult service are to be notified immediately after

    the patient has agreed to come in for transplant. If transplant surgeon on service has concern over

    patient, may contact those services prior to contacting the patient.

    o These services will follow the patient throughout their hospital admission, though SRF will

    remain as the primary service.

    ? Admission orders to follow current protocols (labs, physical exam, OR scheduling, etc)

    ? Medication orders to follow HIV Transplant Protocol

    ? Anticipated transition from transplant surgery to nephrology/ID care will occur around 1 month post-

    transplant

    Post-Transplant

    ? Nephrology and HIV care to be continue at UNC

    ? The patient’s post-transplant coordinator will have primary responsibility for management and

    coordination of care. ? The patient’s HIV Enhanced Care nurse will work with their post-transplant coordinator to maintain

    communication between the two services. It will be their responsibility to work with the appropriate

    attending physicians for patient care.

    ? Labs to follow current UNC protocols. The transplant coordinator is responsible for contacting

    appropriate nephrologist/ID attending with abnormal values and any actions taken. These events are to

    recorded in the TransChart Notes section as well (so as to feed into WebCis).

    o The ID attending/ Enhanced Care nurse may request additional labs/tests as necessary

    ? Both transplant nephrology and ID are responsible for updating patient medication lists in WebCis

    (ID/nephro) and TransChart (nephro)

    ? CD4/ RNA testing to be followed by ID:

    o within 30 days of transplant (pre-transplant to be ordered with admission labs if CRT)

    o at first post-hospital visit (~~10-14 days)

    o with any med changes expected to alter ART levels

    o with any major change in health status ( i.e. hospitalizations)

    o at 60-90 day intervals for 12m after transplant

    o at 90-120 day intervals afterwards if fully suppressed and transplant condition is stable (per HIV

    guidelines)

    ? Additional considerations that would require the transplant coordinator to notify the Enhanced Care

    nurse:

    o Medication changes that may alter ARV concentrations

    o Medication changes that may alter immunosuppressant concentrations

    o Changes to Immunosuppression

    o The ordering of any non-protocol labs/tests (in the event the ID service has additional

    requests/considerations)

    Kidney Transplant HIV Protocol

Induction:

    Antiproliferative: Patient to receive mycophenolate 1000 mg x 1 dose STAT as soon as case is confirmed.

    Steroids: Methylprednisolone 500 mg IVPB x 1 dose STAT tape to chart for intra-op admin.

IL2-RA: Daclizumab 2 mg/kg (round to nearest 25 mg) IVPB x 1 dose on call (product has 4 hour expiration)

    nurse to call pharmacy when patient is called down to the OR. To be administered intra-op. Repeat dose of

    1 mg/kg (round to nearest 25 mg) on POD7.

***Patients are NOT to receive any lymphocyte-depleting induction (thymoglobulin, alemtuzumab, etc) without

    consultation between transplant surgery AND infectious diseases.***

Maintenance:

    Calcineurin inhibitor: Patient to receive tacrolimus starting on POD1. Initiation may be delayed at the

    discretion of the attending on service.

    ? For patients receiving ARVs containing a PI ? NNRTI, the starting dose will be 1 mg PO once. Repeat

    dosing to be based upon goal trough of 8-10 ng/mL. The frequency should NOT exceed twice weekly.

    ? For patients receiving ARVs with a NNRTI, the starting dose will be 1-2 mg PO BID.

    ? For patients not on any ARVs, the starting dose will be 0.05 mg/kg PO BID.

    ? Goal tacrolimus trough concentrations as follows (based upon patient specific parameters):

    o Months 0-3: 8-10 ng/mL

    o Months 3-12: 6-8 ng/mL

    o Months > 12: 5-7 ng/mL

    **For patients who require conversion to cyclosporine, use the following dosing considerations. May adjust up

    or down based upon clinical situation, however the correlation between tacrolimus and cyclosporine dosing is

    not as clear as for patients not on ARVs.:

    ? For patients receiving ARVs containing a PI ? NNRTI, the starting dose will be 25-50 mg PO twice daily.

    ? For patients receiving ARVs with a NNRTI, the starting dose will be 200 450 mg PO BID. Use 200

    mg PO BID if the patient is on nevirapine; use 250 mg PO BID if the patient is on efavirenz.

    ? For patients not on any ARVs, the starting dose will be 4 mg/kg PO BID.

    ? Goal cyclosporine trough concentrations as follows (based upon patient specific parameters):

    o Months 0-3: 250-300 ng/mL

    o Months 3-12: 150-250 ng/mL

    o Months > 12: 100-200 ng/mL

Antiproliferative: Patient to receive mycophenolate mofetil 1000 mg PO BID starting on POD0. Doses may be

    adjusted based upon tolerability and clinical judgement.

Steroids: Follow taper provided below. For patients on PI, patients should be monitored closely for increased

    steroid side effects and potential adrenal insufficiency during the steroid taper. If this becomes problematic,

    consider decreasing the doses and/or slowing the taper down over an extended time interval. For patients on

    an NNRTI, they should be monitored closely for signs & symptoms of rejection.

    POD1 250 mg methylprednisolone

    POD2 -3 125 mg methylprednisolone

    POD4 40 mg prednisone

    POD5 30 mg prednisone

    POD6-13 25 mg prednisone

    POD14-20 20 mg prednisone

    POD21-27 15 mg prednisone

    POD28 10 mg prednisone

    1.5 months post-transplant 7.5 mg prednisone

    2 months post-transplant 5 mg prednisone

Treatment of Rejection

    Treatment of rejection is to be based upon current standard of care, assessing the risk/benefit of any therapies

    utilized. The preferred therapy for cellular rejection is steroid therapy; lymphocyte-depleting agents should be

    administered only after careful consideration, and discussion between transplant surgery, nephrology, and

    infectious diseases. For humoral rejection, the decision to administer rituximab vs IVIG vs plasmapheresis

    should be similarly weighed. All patients should receive ID prophylaxis similar to post-transplant standards

    regardless of treatment modality used.

General Prophylaxis

    GI: Patients not on atazanavir or indinavir are to receive esomeprazole 40 mg PO QHS for stress ulcer

    prophylaxis. For patients on these two ARVs, consultation must be made with the ID service to assess

    risk/benefit of introducing an H-antagonist (requires boosting with ritonavir). 2

CV: Patients are to receive an aspirin 81 mg PO daily starting on POD1.

ID Prophylaxis:

    Surgical: Patients to have cefazolin 1 g x 1 dose ordered on-call to the OR. One dose should be given 6-8

    hours post-operatively as well. For patients with a penicillin allergy, clindamycin 600 mg IVPB may be used in

    place of cefazolin.

PCP: Patients to receive sulfamethoxazole/trimethoprim 800/160 mg PO QMWF. May use dapsone 100 mg

    daily if patient has a sulfa allergy. If patient with sulfa allergy & G6PD deficiency, can consider aerosolized

    pentamidine 300 mg monthly or atovaquone 1500 mg PO daily. This is to be continued for six months after

    transplant or treatment of rejection (including with steroids).

CMV: Prophylaxis as follows:

    ? Low risk: acyclovir 400 mg PO BID x 3 months

    ? Intermediate risk: valganciclovir 450 mg PO daily x 3 months

    ? High risk: valganciclovir 900 mg PO daily x 6 months

    ? Patients with a history of CMV infection are to receive valganciclovir 900 mg PO daily for at least one

    month post-transplant or post-treatment of rejection. If these patients’ CD4 count goes < 100 (outside

    of the immediate post-transplant or post-rejection period), they are to receive valganciclovir until 6

    months after their CD4 count recovers to > 200.

EBV: Patients at high-risk for contracting EBV (donor +/recipient -) to receive ganciclovir 5 mg/kg IV daily

    while in the hospital. They are to continue on valganciclovir 900 mg PO daily x 1 year on discharge. This will

    take the place of CMV prophylaxis in these patients.

Candidiasis: Patient to receive nystatin 10 mL (1,000,000 units) PO TID while on steroids. If CD4 < 200,

    patient is to receive fluconazole 100 mg PO daily.

HIV-specific Prophylaxis:

    MAC: Patients to receive azithromycin 1200 mg PO qweek if CD4 ? 75. Continue until 6 months after CD4 count is > 100. Patients with a history of MAC infection are to receive azithromycin 600 mg PO daily +

    ethambutol 15 mg/kg/day x 1 month post-transplant or post-treatment of rejection. If CD4 ? 75 and patient is not within one month post-transplant or post-rejection period, prophylaxis is to be continued until 6 months

    after their CD4 count recovers to > 100. The use of rifabutin may also be continued by the infectious diseases

    service.

Cryptococcosis, extrapulmonary: Patients with a history of crypto are to receive fluconazole 200 mg PO daily x

    1 month post-transplant or post-treatment of rejection. If these patients have a CD4 count < 200, they are to

    receive prophylaxis until 6 months after their CD4 count recovers to > 200.

Histoplasmosis: Patients with a history of histo are to receive itraconazole 200 mg PO BID (take with food) or

    fluconazole 400 mg PO daily for the rest of their life.

Toxoplasmosis:

    ? If IgG + and CD4 count < 200, patients to receive sulfamethoxazole/trimethoprim 800/160 mg PO daily

    until six months after CD4 count recovers to > 200.

    ? In patients with a history of clinical toxo infection, prophylaxis is to be initiated with pyrimethamine 25

    mg PO daily + sulfadiazine 100 mg/kg PO daily + leucovorin 25 mg PO daily x 1 month post-transplant

    or post-treatment of rejection. If CD4 count < 200, prophylaxis must continue until six months after

    CD4 count recovers to > 200. These patients do not need additional PCP coverage.

    ? In patients with a past infection and a sulfa allergy, prophylaxis is to be pyrimethamine 25 mg PO daily

    + clindamycin 600 mg PO TID. These patients must continue on an additional medication for PCP

    prophylaxis.

    Drug Interactions

    ARVs

    ARV Interacting Transplant Monitoring Considerations Additional Care Measures

    Medications

    NRTIs

    Stavudine (d4T) Mycophenolate Potential for antagonism Try to avoid use of d4T with

    MMF. Monitor for reduced

    effects of MMF

    Zidovudine (ZDV) Mycophenolate Potential for antagonism Try to avoid use of ZDV with

    (also Combivir MMF. Monitor for reduced

    and Trizivir) effects of MMF

    NNRTIs

    Delavirdine (DLV) Cyclosporine, DLV inhibits P450 so may Monitor for increased toxicity

    Tacrolimus, Steroids increase CYA, TAC, and of CYA, TAC and steroids

    steroids

    Efavirenz (EFV) Cyclosporine, EFV induces P450 so will Monitor for rejection

    Tacrolimus, Steroids decrease CYA, TAC, and

    steroids

    Etravirine (ETV) Cyclosporine, ETV inhibits P450 3A and Monitor for rejection

    Tacrolimus, Steroids induces 2C9 and 2C19; may

    decrease CYA, TAC, and

    steroids

    Nevirapine (NVP) Cyclosporine, NVP induces P450 so will Monitor for rejection

    Tacrolimus, Steroids decrease CYA, TAC, and

    steroids

    PIs

    Atazanavir (ATV) - Cyclosporine, ATV inhibits P450 so may Monitor for increased toxicity

     Tacrolimus, Steroids increase CYA, TAC, and of CYA, TAC, steroids, and

    - Mycophenolate (?) steroids; also inhibits UGT MMF

    1A1 so may (but not likely)

    increase MMF (UGT 1A9

    substrate)

    Darunavir/ritonavir Cyclosporine, DRV/RTV inhibits P450 so Monitor for increased toxicity (DRV/RTV) Tacrolimus, Steroids may increase CYA, TAC, and of CYA, TAC, steroids

     steroids

    Fosamprenavir Cyclosporine, FPV induces P450 so may - Monitor for rejection OR (FPV) Tacrolimus, Steroids decrease CYA, TAC, and - Monitor for increased

     steroids; however, with RTV toxicity of CYA, TAC,

    likely inhibits 3A4 so may steroids, and MMF

    increase CYA, TAC, and

    steroids

    Indinavir (IDV) Cyclosporine, IDV inhibits P450 so may Monitor for increased toxicity

    Tacrolimus, Steroids increase CYA, TAC, and of CYA, TAC, steroids

     steroids

    Lopinavir/ritonavir Cyclosporine, LPV/RTV inhibits P450 3A Monitor for increased toxicity (LPV/RTV) Tacrolimus, Steroids and induces 1A2, 2C9, and of CYA, TAC, steroids

     2C19

    Nelfinavir (NFV) Cyclosporine, NFV inhibits P450 so may Monitor for increased toxicity

    Tacrolimus, Steroids increase CYA, TAC, and of CYA, TAC, steroids

     steroids

    Ritonavir (RTV) Cyclosporine, Low doses of RTV (100-Monitor for increased toxicity

    Tacrolimus, Steroids 200mg QD-BID) potently of CYA, TAC, steroids

     inhibits P450 so will increase

    CYA, TAC, and steroids

    Saquinavir (SQV) Cyclosporine, SQV inhibits P450 so may Monitor for increased toxicity

    Tacrolimus, Steroids increase CYA, TAC, and of CYA, TAC, steroids

     steroids

    Tipranavir/ritonavir Cyclosporine, TPV/RTV inhibits 3A so may Monitor for increased toxicity (TPV/RTV) Tacrolimus, Steroids increase CYA, TAC, and of CYA, TAC, steroids

     steroids

    Other Therapies Interacting ARV Monitoring Considerations Additional Care Measures Acid Suppression Agents

    Proton Pump Atazanavir and ATV and IDV have pH Avoid concomitant use. If Inhibitors Indinavir dependent absorption so use is required page HIV

    PPIs interact provider.

    H2-blockers Atazanavir and ATV and IDV have pH ? Do not use w/o RTV. (Ranitidine, etc) Indinavir dependent absorption so H2 ? Do not use more than dose

    blockers interact equivalent of famotidine

    40mg BID

    ? ATV 300mg + RTV 100mg

    should be given

    simultaneously or ? 10 hrs

    after H2 blocker

    ? In ARV experienced pts

    also taking tenofovir, use

    ATV 400mg + RTV 100mg

    QD Antiepileptics Phenytoin, Avoid concomitant use with ? NNRTIs and PIs ? These antiepileptics greatly

    Phenobarbital, ARVs decrease rx concentrations ? CSA, FK, Rapa

    carbamazepine, ? Monitor trough values of

    oxcarbazepine anti-rejection meds closely Antifungals Ketoconazole, ? NNRTIs and PIs ? Keto and itra may increase ? Monitor for toxicity of both itraconzole ARV concentrations and azole and ARVs ? CSA, FK, Rapa

    vice versa ? Monitor CSA, FK, & Rapa

    ? Will increase levels of anti-troughs closely

    rejection meds

    Voriconazole ? NNRTIs and PIs ? If concomitant use is ? Vori may increase ARVs &

    required consult with ID antirejection meds ? CSA, FK, Rapa

    ? Avoid use with Rapa ? NNRTIs may decrease Vori

    ? Decrease CSA & FK to ? PIs may increase Vori

    25-30% of starting doses Fluconazole CSA, FK, Rapa Fluc will increase ? Decrease doses to 50% of

    antirejection meds starting doses if on 400

    mg (or renally dosed

    equivalent)

    ? For doses < 400 mg, can

    monitor trough levels

    closely or empirically

    decrease doses by < 50% Antihypertensives Calcium channel Atazanavir ATV can prolong QT interval. If used concomitantly with blockers CCB baseline EKG is

    suggested. Non-Diltiazem & verapamil can Monitor trough levels closely ? FK, CSA, Rapa

    dihydropyridine increase levels

    CCBs

    Beta-blockers Protease inhibitors Pis may increase some beta-Atenolol is OK to use. (metoprolol, (especially RTV) blockers

    propranolol)

    Antituberculosis Meds

    Rifampin RIF will decrease these ? NNRTIs and PIs ? If use is required consult

    meds with ID. ? CSA, FK, Rapa

    ? Monitor trough levels

    closely with anti-rejection

    meds

Rifabutin ? NNRTIs and PIs ? Dose adjustments for RBT ? RBT usually has little effect

    on ARVs are needed for ? CSA, FK, Rapa

    concomitant use with ? NNRTIs decrease RBT

    NNRTIs and PIs. ? PIs increase RBT

    ? Consult ID ? May decrease levels of

    ? Monitor trough levels antirejection meds

    closely with anti-rejection

    meds Asthma Therapies Inhaled or nasal Protease inhibitors PIs can greatly increase If inhaled steroid needed steroids (especially RTV) inhaled steroid consider beclomethasone or

    concentrations systemically budesonide (no data for

    (most data with fluticasone) this). If fluticasone required

    monitor cortisol reqularly. Long acting beta Protease inhibitors PIs may increase LABAs Monitor for toxicity of LABA blockers (especially RTV) or avoid concomitant use (salmeterol,

    formoterol)

    Benzodiazepines Midazolam, Protease inhibitors PIs are contraindicated with Avoid concomitant use triazolam (especially RTV) these BDZs

    Erectile Dysfunction Meds

    Sildenfafil, All of these medications will Dose modifications for ED ? Protease inhibitors

    Tadalafil, increase concentrations of meds are required. Do not (especially RTV)

    Vardenafil ED meds. start at more than 25 mg of ? CSA, FK, RAPA

    sildenafil (or the equivalent) HMG CoA reductase

    inhibitors

    Simvastatin, Efavirenz, nevirapine, EFV, NVP, and ETR may Higher doses of statins will lovastatin, and etravirine (NNRTIs) decrease exposure to statins likely be needed. fluvastatin, (except rosuvastatin).

    pravastatin,

    atorvastatin

    Simvastatin, Protease inhibitors PIs greatly increase these Do not use concomitantly lovastatin, (especially RTV) particular statins with PIs. fluvastatin, OK to use pravastatin, Atorvastatin >20mg atorvastatin up to 20mg QD, QD and rosuvastatin Simvastatin, CSA, FK, RAPA These medications may Do not use more than 40 mg lovastatin, increase exposure to statins. of any of these. Okay to use fluvastatin, atorvastatin 40 mg unless on atorvastatin PI (see above)

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