Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 7, Issue 12, Pages 2816-2820Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1600-6143.2007.02007.x
Keywords
dose modification; HIV; immunosuppressant pharmacokinetics; kidney transplantation; liver transplantation
Categories
Funding
- NIAID NIH HHS [U01 AI052748-01] Funding Source: Medline
- PHS HHS [M01 00079] Funding Source: Medline
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Solid organ transplantation in human immunodeficiency virus (HIV)-infected individuals requiring concomitant use of immunosuppressants (IS) (e.g. cyclosporine [CsA], sirolimus [SrL], tacrolimus [FK]) and antiretrovirals (ARVs) (e.g. protease inhibitors [PIs] and/or nonnucleoside reverse transcriptase inhibitors [NNRTIs]) is complicated by significant drug interactions. To assist in appropriate clinical management, we describe the pharmacokinetics and dosing modifications in 35 patients (20 kidney, 13 liver and two kidney-liver HIV-infected subjects with end-stage kidney or liver disease), on both IS and NNRTIs, PIs, and combined NNRTIs + PIs, in studies done at weeks 2-4 and/or 12 weeks after transplantation or after a change in IS or ARV drug regimen (n = 97 studies). CsA, SrL and FK concentrations were measured in whole blood by LC/MS. HIV-infected transplant recipients using PIs with IS had marked increases in CsA, FK or SrL trough levels compared to those on NNRTIs alone or to patients not on ARVs, necessitating either a reduction in dose or an increase in dosing interval. Subjects on efavirenz (EFV) and CsA required much higher doses of CsA than those using any other ARV. Changes in antiretroviral therapy should be carefully managed to avoid insufficient immunosuppression or toxicity due to drug interactions.
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