Download IMPROVING PHARMACEUTICAL MANAGEMENT OF HIV

IMPROVING PHARMACEUTICAL MANAGEMENT OF HIV PATIENTS LISTED
FOR A TRANSPLANT
BACKGROUND: Patients with HIV disease are at an increased risk for the development of
chronic kidney disease (CKD) and consequently end-stage renal failure (ESRF). Patients with
HIV- associated nephropathy (HIVAN) are also a high risk of cardiovascular events and death.
Recent times have seen many substantial advances in antiretroviral (ARV) therapy and an
improvement in the management of opportunistic infections. HIV is therefore no longer a
contraindication for a solid organ transplant. As a result, many renal units are seeing an increase
in the number of renal and/or pancreatic transplants within this cohort of patients. Concomitant
use of immunosuppressants such as tacrolimus and mycophenolate mofetil with protease
inhibitors (PI) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) have the potential to
interact. The mechanism of interactions can vary from the induction/ inhibition of either the
CYP450 enzyme pathway or p-glycoprotein transporters. When using a ritonavir boosted ARV
regimen dramatic increases in CNI and mTOR exposures, requiring significant dose reductions
and increased dose intervals. Management of these interactions is very complex and requires
very close therapeutic drug monitoring alongside good patient compliance and understanding of
their medicines. Experience has taught us that the risk of rejection is high in these patients and a
fine balance needs to be maintained between immunosuppressing the patient post-transplant and
controlling viral replication. It is imperative to manage any drug-drug interactions so as to
reduce the risk of nephrotoxicity and acute rejection of the new graft. In March 2015, BTS and
BHIVA issued joint updated guidance for kidney and pancreas transplantation with HIV. It
recommends that the most appropriate anti-retroviral therapy should be determined before
transplantation in conjunction with an HIV specialist in order to anticipate potential drug
interactions and appropriate dosing of medications. Pre-emptive switching is recommended,
away from PI based ARV regimens, especially those including ritonavir. ARVs with a
nephrotoxic potential such as tenofovir or abacavir should also be avoided if alternatives are
available.
RATIONALE: This proforma is designed to review the patient’s current medications (all
prescribed and non-prescribed) alongside medications that would be prescribed during and after
the transplantation. The aim is to (1) ensure a suitable pharmaceutical management plan is in
place and available to the transplant team prior to the transplant preventing harm to the patient,
(2) Identify any potential drug-drug interactions, and work out possible solutions to preventing
any adverse effects post-transplant (3) Ensure that the patient receives optimal doses of CNIs
(tacrolimus) to as to reduce any risk of graft rejection. This is carried out in a multi-disciplinary
setting between the renal and HIV physicians and pharmacy team, patient and GP (at patient
consent).
PROCESS: Low clearance clinics and dialysis units (haemodialysis and peritoneal dialysis)
were informed about the proforma, who then identified the appropriate patients wait-listed for
transplantation (active or suspended). With patient consent, the unit then complete the referral
form and submit to the renal pharmacy team. Renal pharmacist to complete an enquiry for this
patient, looking at the following details (1) Identification of any drug-drug interactions, (2)
Identification of any nephrotoxic agents, (3) Dose adjustments for ARV therapy once renal
function improves post-transplant. A management plan is put in place with recommendations
made and appropriate clinicians informed
GOING FORWARD: The renal pharmacy team are looking to enrol each patient with HIV
awaiting a transplant to this program. Each proforma will be reviewed and updated every 6
months or earlier if any changes are made. Each proforma will be looked at in a
multidisciplinary setting so that the management of these complex patients can be smooth and
effective, hopefully reducing the patient’s overall risk of graft rejection and viral resistance.