Differential Dose Adjustments of Immunosuppressants after Resuming Boosted versus Unboosted HIV-Protease Inhibitors Postliver Transplant

Pharmacokinetic (PK) interactions between protease inhibitors (PIs) and immunosuppressive agents (IS) are critical elements in the management of HIV-infected patients who undergo liver transplantation (LTx). The primary objective of this study was to evaluate the decreases in IS dosages necessary to maintain an appropriate therapeutic window (TW) after initiating PI-based antiretroviral therapy regimens post-LTx. Single-center, PK cross-sectional study of consecutive HIV-infected adult patients who underwent LTxwas done. Blood trough concentrations (Ct) of IS were obtained using a commercial MEIA test; plasma Ctof PIswere measured using HPLC. Twelve consecutive HIV-infected adult patients (11 males, 1 female) were enrolled. More rapid increases in IS plasma Ctwere observed 48 h after initiating ritonavir (RTV)-boosted PI therapy post-LTxthan when using unboosted PIs. Seven patients developed acute renal failure. The median fold decrease in IS dosages required to regain IS concentrations that were in the TW was 7.5 (range 6–14) after resuming boosted PIsand 2.9 (range 2–4) after unboosted PIs. The overall median time necessary to reach IS TW after dose adjustment was 3.5 days (range 0–15). Unboosted PIsexhibited lesser PK interactions with IS than did RTV-boosted PIsand were thus more amenable to use in the post-LTxsetting.