Differential dose adjustments of immunosuppressants after resuming boosted versus unboosted HIV-protease inhibitors postliver transplant.
Pharmacokinetic (PK) interactions between protease inhibitors (PI(s)) and immunosuppressive agents (IS) are critical elements in the management of HIV-infected patients who undergo liver transplantation (LT(x)). 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-LT(x). Single-center, PK cross-sectional study of consecutive HIV-infected adult patients who underwent LT(x) was done. Blood trough concentrations (C(t)) of IS were obtained using a commercial MEIA test; plasma C(t) of PI(s) were measured using HPLC. Twelve consecutive HIV-infected adult patients (11 males, 1 female) were enrolled. More rapid increases in IS plasma C(t) were observed 48 h after initiating ritonavir (RTV)-boosted PI therapy post-LT(x) than when using unboosted PI(s). 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 PI(s) and 2.9 (range 2-4) after unboosted PI(s). The overall median time necessary to reach IS TW after dose adjustment was 3.5 days (range 0-15). Unboosted PI(s) exhibited lesser PK interactions with IS than did RTV-boosted PI(s) and were thus more amenable to use in the post-LT(x) setting.
Guaraldi
G
G
Clinic of Infectious Diseases, Department of Internal Medicine and Medical Specialties, University of Modena and Reggio Emilia, Modena, Italy. g.guaraldi@unimore.it
Cocchi
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Motta
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Ciaffi
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Conti
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Codeluppi
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Bonora
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Zona
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Di Benedetto
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Pinetti
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D'Avolio
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Bertolini
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Esposito
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D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000601:surgery; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged
D017320:HIV Protease Inhibitors; D007166:Immunosuppressive Agents