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Immunosuppressants and Antiretroviral Therapy in HIV-Positive Transplant Patients 

Immunosuppressants and Antiretroviral Therapy in HIV-Positive Transplant Patients
Chapter:
Immunosuppressants and Antiretroviral Therapy in HIV-Positive Transplant Patients
Author(s):

Carolyn Kramer

and Emily Blumberg

DOI:
10.1093/med/9780190493097.003.0028
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date: 29 October 2020

Protease inhibitors (PIs), especially ritonavir, are inhibitors of CYP3A4 and P-gp1 and can significantly increase levels of calcineurin inhibitors and mammalian target of rapamycin (mTOR) inhibitors. Cobicistat is an inhibitor of CYP3A4, and its effect on levels of calcineurin inhibitors and mTOR inhibitors is likely to be similar to that of ritonavir. Efavirenz may result in lower concentrations of calcineurin inhibitors and mTOR inhibitors. Dose reduction and careful attention to monitoring drug levels are critical to avoid toxicity and maintain therapeutic immunosuppressive concentrations when PIs or cobicistat are coadministered with calcineurin inhibitors or mTOR inhibitors. Although there is no formalized recommendation for the ideal antiretroviral therapy regimen in HIV-positive transplant recipients, a regimen consisting of two nucleoside reverse transcriptase and an integrase inhibitor minimizes the risk of drug–drug interactions and simplifies dosing of immunosuppressive agents while maintaining a high barrier to resistance.

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