Reduced raltegravir clearance in HIV-infected liver transplant recipients: an unexpected interaction with immunosuppressive therapy?

Liver transplantation (LTx) is considered a safe procedure in selected HIV-infected patients. In this clinical setting raltegravir is the antiretroviral of choice due to its optimal tolerability and its negligible interactions with immunosuppressive drugs. We aimed at providing data on the pharmacokinetics of raltegravir in LTx recipients, on which the available information is inconclusive. In this retrospective multicentre study we characterized the pharmacokinetics of raltegravir in a consecutive series of HIV-infected LTx recipients referred to our laboratory for therapeutic drug monitoring (TDM) and compared the obtained profiles with those collected from a control group of HIV-infected patients. Seventeen HIV-infected LTx patients were considered. LTx recipients had significantly higher raltegravir AUC(0-12) compared with the control group of HIV-infected patients [14aEuroS314 (11aEuroS627-19aEuroS998) versus 8795 (5218-12aEuroS954) ng center dot h/mL; PaEuroS < aEuroS0.01]. Two LTx patients experienced moderate increments in serum transaminases, nausea and vomiting that improved after raltegravir dose reduction. High raltegravir exposure and acceptable safety profile were observed in HIV-infected LTx recipients. Our results highlight that some patients may obtain an advantage from TDM-guided raltegravir dose adjustments with potential benefits in terms of drug tolerability.