Solid organ transplantation in human immunodeficiency virus (HIV)-infected individuals requiring con) 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.

Background Interactions between antiretrovirals (ARVs) and transplant immunosuppressant agents (IS) among HIV-infected transplant recipients may lead to lack of efficacy or toxicity. In transplant recipients not infected with HIV, cyclosporine (CsA) and tacrolimus (TAC) trough levels (C0) or those drawn two hours after dosing (C2) correlate with drug exposure (AUC/dose) and outcomes. Due to ARV-IS interactions in HIV-infected individuals, and the high rate of rejection in these subjects, we investigated the correlations between IS concentrations and exposure to determine the best method to monitor immunosuppressant levels. Methods We prospectively studied 50 HIV-infected transplant recipients undergoing kidney or liver transplantation evaluating the pharmacokinetics of the IS over time after transplantation (weeks 2 to 4, 12, 28, 52, and 104). IS levels were measured with LC/MS/MS and AUC calculated using WinNonLin 9.0. Correlation analyses were run on SAS 9.2 Results CsA concentration at C4 correlated better with AUC than C0 or C2, and TAC concentration correlated better at C0 or C2. Conclusions We suggest that C0 is acceptable for TAC monitoring, but poor predictability will occur at C0 with CsA. The low correlation of C0 with CsA AUC could be responsible for the higher rejection rates on CsA that has been reported in these subjects.