Drug–Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation: A Review

1 Department of Clinical Pharmacy, University Medical Center Utrecht , The Netherlands .
AIDS patient care and STDs (Impact Factor: 3.5). 10/2012; 26(10):568-81. DOI: 10.1089/apc.2012.0169
Source: PubMed


Abstract Since the introduction of combination antiretroviral therapy (cART) resulting in the prolonged survival of HIV-infected patients, HIV infection is no longer considered to be a contraindication for solid organ transplantation (SOT). The combined management of antiretroviral and immunosuppressive therapy proved to be extremely challenging, as witnessed by high rates of allograft rejection and drug toxicity, but the profound drug-drug interactions between immunosuppressants and cART, especially protease inhibitors (PIs) also play an important role. Caution and frequent drug level monitoring of calcineurin inhibitors, such as tacrolimus are necessary when PIs are (re)introduced or withdrawn in HIV-infected recipients. Furthermore, the pharmacokinetics of glucocorticoids and mTOR inhibitors are seriously affected by PIs. With the introduction of integrase inhibitors, CCR5-antagonists and fusion inhibitors which cause significantly less pharmacokinetic interactions, have minor overlapping toxicity, and offer the advantage of pharmacodynamic synergy, it is time to revaluate what may be considered the optimal antiretroviral regimen in SOT recipients. In this review we provide a brief overview of the recent success of SOT in the HIV population, and an update on the pharmacokinetic and pharmacodynamic interactions between currently available cART and immunosuppressants in HIV-infected patients, who underwent SOT.

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    • "Clinical experience indicates that patients on PI may require only 1e2 mg of TAC per week to keep therapeutic levels [20]. Patients on a ritonavir-boosted PI regimen can require even lower doses of CNIs [20]. In our experience the dose of TAC in patients with darunavir boosted by ritonavir (Table 2, patients 1 to 3) was 0.5 mg/d each 7e10 days. "
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