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 posttransplant
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 H2-antagonist (requires boosting with ritonavir).
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
NRTIs
Stavudine (d4T)
Zidovudine (ZDV)
(also Combivir
and Trizivir)
NNRTIs
Interacting Transplant
Medications
Monitoring Considerations
Mycophenolate
Potential for antagonism
Mycophenolate
Potential for antagonism
Additional Care Measures
Try to avoid use of d4T with
MMF. Monitor for reduced
effects of MMF
Try to avoid use of ZDV with
MMF. Monitor for reduced
effects of MMF
Delavirdine (DLV)
Cyclosporine,
Tacrolimus, Steroids
Efavirenz (EFV)
Cyclosporine,
Tacrolimus, Steroids
Etravirine (ETV)
Cyclosporine,
Tacrolimus, Steroids
Nevirapine (NVP)
Cyclosporine,
Tacrolimus, Steroids
PIs
Atazanavir (ATV)
- Cyclosporine,
Tacrolimus, Steroids
- Mycophenolate (?)
Darunavir/ritonavir
(DRV/RTV)
Cyclosporine,
Tacrolimus, Steroids
Fosamprenavir
(FPV)
Cyclosporine,
Tacrolimus, Steroids
Indinavir (IDV)
Cyclosporine,
Tacrolimus, Steroids
Lopinavir/ritonavir
(LPV/RTV)
Cyclosporine,
Tacrolimus, Steroids
Nelfinavir (NFV)
Cyclosporine,
Tacrolimus, Steroids
Ritonavir (RTV)
Cyclosporine,
Tacrolimus, Steroids
Saquinavir (SQV)
Cyclosporine,
Tacrolimus, Steroids
Tipranavir/ritonavir Cyclosporine,
(TPV/RTV)
Tacrolimus, Steroids
Other Therapies
Acid Suppression
Agents
Proton Pump
Inhibitors
Interacting ARV
Atazanavir and
Indinavir
DLV inhibits P450 so may
increase CYA, TAC, and
steroids
EFV induces P450 so will
decrease CYA, TAC, and
steroids
ETV inhibits P450 3A and
induces 2C9 and 2C19; may
decrease CYA, TAC, and
steroids
NVP induces P450 so will
decrease CYA, TAC, and
steroids
Monitor for increased toxicity
of CYA, TAC and steroids
ATV inhibits P450 so may
increase CYA, TAC, and
steroids; also inhibits UGT
1A1 so may (but not likely)
increase MMF (UGT 1A9
substrate)
DRV/RTV inhibits P450 so
may increase CYA, TAC, and
steroids
FPV induces P450 so may
decrease CYA, TAC, and
steroids; however, with RTV
likely inhibits 3A4 so may
increase CYA, TAC, and
steroids
IDV inhibits P450 so may
increase CYA, TAC, and
steroids
LPV/RTV inhibits P450 3A
and induces 1A2, 2C9, and
2C19
NFV inhibits P450 so may
increase CYA, TAC, and
steroids
Low doses of RTV (100200mg QD-BID) potently
inhibits P450 so will increase
CYA, TAC, and steroids
SQV inhibits P450 so may
increase CYA, TAC, and
steroids
TPV/RTV inhibits 3A so may
increase CYA, TAC, and
steroids
Monitor for increased toxicity
of CYA, TAC, steroids, and
MMF
Monitoring Considerations
Additional Care Measures
ATV and IDV have pH
dependent absorption so
PPIs interact
Monitor for rejection
Monitor for rejection
Monitor for rejection
Monitor for increased toxicity
of CYA, TAC, steroids
- Monitor for rejection OR
- Monitor for increased
toxicity of CYA, TAC,
steroids, and MMF
Monitor for increased toxicity
of CYA, TAC, steroids
Monitor for increased toxicity
of CYA, TAC, steroids
Monitor for increased toxicity
of CYA, TAC, steroids
Monitor for increased toxicity
of CYA, TAC, steroids
Monitor for increased toxicity
of CYA, TAC, steroids
Monitor for increased toxicity
of CYA, TAC, steroids
Avoid concomitant use. If
use is required page HIV
provider.
H2-blockers
(Ranitidine, etc)
Antiepileptics
Phenytoin,
Phenobarbital,
carbamazepine,
oxcarbazepine
Antifungals
Ketoconazole,
itraconzole
Atazanavir and
Indinavir
ATV and IDV have pH
dependent absorption so H2
blockers interact
 Do not use w/o RTV.
 Do not use more than dose
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
 NNRTIs and PIs
 CSA, FK, Rapa
 These antiepileptics greatly
decrease rx concentrations
 Monitor trough values of
anti-rejection meds closely
Avoid concomitant use with
ARVs
 NNRTIs and PIs
 CSA, FK, Rapa
 Keto and itra may increase
ARV concentrations and
vice versa
 Will increase levels of antirejection meds
 Vori may increase ARVs &
antirejection meds
 NNRTIs may decrease Vori
 PIs may increase Vori
 Monitor for toxicity of both
azole and ARVs
 Monitor CSA, FK, & Rapa
troughs closely
Voriconazole
 NNRTIs and PIs
 CSA, FK, Rapa
Fluconazole
CSA, FK, Rapa
Antihypertensives
Calcium channel
Atazanavir
blockers
Nondihydropyridine
CCBs
Beta-blockers
(metoprolol,
propranolol)
Antituberculosis
Meds
Rifampin
Fluc will increase
antirejection meds
ATV can prolong QT interval.
 If concomitant use is
required consult with ID
 Avoid use with Rapa
 Decrease CSA & FK to
25-30% of starting doses
 Decrease doses to 50% of
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%
If used concomitantly with
CCB baseline EKG is
suggested.
Monitor trough levels closely
 FK, CSA, Rapa
Diltiazem & verapamil can
increase levels
Protease inhibitors
(especially RTV)
Pis may increase some betablockers
Atenolol is OK to use.
 NNRTIs and PIs
 CSA, FK, Rapa
RIF will decrease these
meds
 If use is required consult
with ID.
 Monitor trough levels
closely with anti-rejection
meds
Rifabutin
 NNRTIs and PIs
 CSA, FK, Rapa
Asthma Therapies
Inhaled or nasal
Protease inhibitors
steroids
(especially RTV)
Long acting beta
blockers
(salmeterol,
formoterol)
Benzodiazepines
Midazolam,
triazolam
Erectile
Dysfunction Meds
Sildenfafil,
Tadalafil,
Vardenafil
HMG CoA
reductase
inhibitors
Simvastatin,
lovastatin,
fluvastatin,
pravastatin,
atorvastatin
Simvastatin,
lovastatin,
fluvastatin,
Atorvastatin >20mg
QD
Simvastatin,
lovastatin,
fluvastatin,
atorvastatin
 RBT usually has little effect
on ARVs
 NNRTIs decrease RBT
 PIs increase RBT
 May decrease levels of
antirejection meds
 Dose adjustments for RBT
are needed for
concomitant use with
NNRTIs and PIs.
 Consult ID
 Monitor trough levels
closely with anti-rejection
meds
PIs can greatly increase
inhaled steroid
concentrations systemically
(most data with fluticasone)
If inhaled steroid needed
consider beclomethasone or
budesonide (no data for
this). If fluticasone required
monitor cortisol reqularly.
Monitor for toxicity of LABA
or avoid concomitant use
Protease inhibitors
(especially RTV)
PIs may increase LABAs
Protease inhibitors
(especially RTV)
PIs are contraindicated with
these BDZs
Avoid concomitant use
 Protease inhibitors
(especially RTV)
 CSA, FK, RAPA
All of these medications will
increase concentrations of
ED meds.
Dose modifications for ED
meds are required. Do not
start at more than 25 mg of
sildenafil (or the equivalent)
Efavirenz, nevirapine,
and etravirine (NNRTIs)
EFV, NVP, and ETR may
decrease exposure to statins
(except rosuvastatin).
Higher doses of statins will
likely be needed.
Protease inhibitors
(especially RTV)
PIs greatly increase these
particular statins
CSA, FK, RAPA
These medications may
increase exposure to statins.
Do not use concomitantly
with PIs.
OK to use pravastatin,
atorvastatin up to 20mg QD,
and rosuvastatin
Do not use more than 40 mg
of any of these. Okay to use
atorvastatin 40 mg unless on
PI (see above)