Background:  Today, there are no clear recommendations regarding ART doses before and after orthoptic liver transplantation (OLT). It is a complex subject mainly because of the length of the waiting list for transplant, and of the drug interactions between some post-OLT treatments (e.g., calcineurin inhibitors) and ART drugs (e.g., protease inhibitors [PI] or non-nucleoside reverse transcriptase inhibitors [NNRTI]), which may be deleterious for the grafted liver (e.g., drug-induced steatosis and PI-induced liver toxicity). Enfuvirtide (ENF) is an ART drug not metabolized by CYP450. Our objective was to appraise the benefit of ENF within the treatments prescribed to HIV/hepatitis B virus (HBV)- or hepatitis C virus (HCV)-co-infected patients, before and after OLT.

Methods:  Since 1999, 41 HIV-co-infected patients underwent an OLT in our center. This retrospective pilot study focused on the patients treated by ENF prior and/or after OLT. ENF, 90 mg twice daily, was given in combination with 2 other ART drugs (NNRTI and/or NRTI). Monthly assessments consisted of CD4 cell count, HIV plasma viral load, liver function tests, and safety outcomes.

Results:  We have been treated with ENF, 6 HIV/HCV- and 2 HIV/HBV-co-infected patients. All patients received tacrolimus with a dose adjustment in order to reach a blood concentration range of 10 to 15 ng/mL; 4 patients were treated by ENF prior to OLT (median duration: 13 months; range 6 to 17). At ENF initiation, HIV load was undetectable (mean <400 copies/mL) and median CD4 151 cells/µL (65 to 190), Child-Pugh class C; median MELD score, 40 (35 to 40). No deterioration of hepatic deficiency was observed in either biochemical or clinical parameters before OLT, enabling all patients to be recently transplanted. Four patients received ENF only after OLT. At ENF initiation, median CD4 was 187 cells/µL (60 to 300), and HIV load was undetectable. At 3 months, median CD4 remained stable (280 cells/µL, 130 to 400), and HIV load undetectable. ENF treatment was stopped at patients’ request (local intolerance to injections), at a median time of 7 months (2 to 12) after OLT. At this time, median CD4 was 252 cells/µL (130 to 400), HIV load remained undetectable and liver function was normal. No severe adverse event related to ENF has been reported. ENF treatment did not lead to any change in tacrolimus pharmacokinetics.

Conclusions:  This pilot study shows that ENF tends not to change tacrolimus pharmacokinetics and may be an alternative to address the drug interaction toxicity issue in HIV-co-infected patients undergoing OLT. Such results deserve confirmation trials.