Immunosuppressant pharmacokinetics and dosing modifications in HIV-1 infected liver and kidney transplant recipients.
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.
Frassetto
L A
LA
Department of Medicine, Clinical Research Center, University of California, San Francisco, CA, USA.
Browne
M
M
Cheng
A
A
Wolfe
A R
AR
Roland
M E
ME
Stock
P G
PG
Carlson
L
L
Benet
L Z
LZ
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000472:pathogenicity; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007668:Kidney / Q000601:surgery / Q000821:virology; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008099:Liver / Q000601:surgery / Q000821:virology; D008107:Liver Diseases / Q000601:surgery; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use
D044966:Anti-Retroviral Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus