Teicher Elina, Abbara Chadi, Duclos-Vallée Jean-Charles, Antonini Teresa, Bonhomme-Faivre Laurence, Desbois Delphine, Samuel Didier, Vittecoq Daniel
Département Médecine Interne et Infectiologie, AP-HP Hôpital Paul Brousse, Villejuif, France.
Liver Transpl. 2009 Oct;15(10):1336-42. doi: 10.1002/lt.21818.
The aim of this study was to evaluate the impact of an enfuvirtide-based antiretroviral (ARV) regimen on the management of immunosuppression and follow-up in hepatitis C virus (HCV)/hepatitis B virus (HBV)/human immunodeficiency virus (HIV)-coinfected liver transplant patients in comparison with a lopinavir/ritonavir-based ARV regimen. Tacrolimus and cyclosporine trough concentrations were determined at a steady state during 3 periods: after liver transplantation without ARV treatment (period 1), at the time of ARV reintroduction (period 2), and 2 to 3 months after liver transplantation (period 3). The findings for 22 HIV-coinfected patients were compared (18 with HCV and 4 with HBV); 11 patients were treated with enfuvirtide and were matched with 11 lopinavir/ritonavir-exposed patients. During period 1, tacrolimus and cyclosporine A doses were 8 and 600 mg/day, respectively, and the trough concentrations were within the therapeutic range in both groups. In period 2, the addition of lopinavir/ritonavir to the immunosuppressant regimen enabled a reduction in the dose of immunosuppressants required to maintain trough concentrations within the therapeutic range (to 0.3 mg/day for tacrolimus and 75 mg/day for cyclosporine). Immunosuppressant doses were not modified by the reintroduction of enfuvirtide, there being no change in the mean trough concentrations over the 3 periods. CD4 cell counts remained at about 200 cells/mm3. The HIV RNA viral load remained undetectable. Both groups displayed signs of mild cytolysis and cholestasis due to the recurrence of HCV, whereas no renal insufficiency was observed. Enfuvirtide is an attractive alternative to standard ARV therapy, facilitating the management of drug-drug interactions shortly after liver transplantation. Moreover, the lack of liver toxicity renders this drug valuable in the event of a severe HCV recurrence.
本研究旨在评估与基于洛匹那韦/利托那韦的抗逆转录病毒（ARV）方案相比，基于恩夫韦肽的ARV方案对丙型肝炎病毒（HCV）/乙型肝炎病毒（HBV）/人类免疫缺陷病毒（HIV）合并感染的肝移植患者免疫抑制管理及随访的影响。在3个阶段的稳态期测定他克莫司和环孢素的谷浓度：肝移植后未进行ARV治疗时（阶段1）、重新引入ARV时（阶段2）以及肝移植后2至3个月（阶段3）。比较了22例HIV合并感染患者的结果（18例合并HCV，4例合并HBV）；11例患者接受恩夫韦肽治疗，并与11例接受洛匹那韦/利托那韦治疗的患者配对。在阶段1，他克莫司和环孢素A的剂量分别为8和600mg/天，两组的谷浓度均在治疗范围内。在阶段2，在免疫抑制方案中添加洛匹那韦/利托那韦能够降低将谷浓度维持在治疗范围内所需的免疫抑制剂剂量（他克莫司降至0.3mg/天，环孢素降至75mg/天）。重新引入恩夫韦肽未改变免疫抑制剂剂量，3个阶段的平均谷浓度无变化。CD4细胞计数维持在约200个细胞/mm³。HIV RNA病毒载量仍未检测到。由于HCV复发，两组均出现轻度细胞溶解和胆汁淤积的迹象，而未观察到肾功能不全。恩夫韦肽是标准ARV治疗的一个有吸引力的替代方案，有助于肝移植后不久药物相互作用的管理。此外，缺乏肝毒性使得该药物在严重HCV复发时具有价值。
