Tacrolimus Exposure and Its Relation With Clinical Outcomes in HIV Infected Kidney Transplant Recipients On Antiretroviral Agents: An Area-Under-The-Curve Driven Analysis.

To study tacrolimus (TAC) exposure in detail and investigate its relation with clinical outcomes in HIV infected kidney transplant recipients (KTRs) on antiretroviral agents. Methods Data were extracted from the prospective NIH-sponsored trial AI052748 and a rich within-population pharmacokinetic (PK) data set. HIV KTRs receiving TAC and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) within one year posttransplant were included. PK models were designed to determine TAC area-under-the-curves (AUCs). TAC levels and AUCs were compared between KTRs receiving PIs or NNRTIs. Univariate and multivariate analyses were used to test the associations between Tac levels or AUCs and the risk of acute rejection. Results 53 KTRs on an NNRTI and 40 KTRs on a PI were included. The mean daily AUC of TAC was 44% lower in KTRs on PIs compared to NNRTIs (12.1 vs 17.4 ng*day/L, p<0.01), while their mean TAC level was higher (10.5 vs 8.5 ng/mL, p<0.01).Figure: No Caption available.The mean daily AUC in KTRs who experienced an acute rejection episode was lower compared to KTRs who did not (12.1 vs 16.1 ng*day/mL, p=0.026). A higher mean daily AUC (HR=0.89; 95% CI: 0.82-0.97; p=0.01) and higher TAC trough level (HR=0.92; 95% CI: 0.85-0.997; p=0.04) were each associated with a lower risk of acute rejection. Conclusions In HIV infected kidney transplant recipients TAC exposure is strongly affected by their antiretroviral regimen. Thereby and because of a signficant AUC-rejection association, AUC monitoring should be considered in these patients.