Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia, Modena, Italy.
Transplantation. 2010 Mar 27;89(6):733-8. doi: 10.1097/TP.0b013e3181c7dcc0.
Some experimental trials have demonstrated that rapamycin (RAPA) is able to inhibit HIV-1 progression in three different ways: (1) reducing CCR5-gene transcription, (2) blocking interleukin-2 intracellular secondary messenger (mammalian target of rapamycin), and (3) up-regulating the beta-chemokine macrophage inflammatory protein (MIP; MIP-1alpha and MIP-1beta). We present the preliminary results of a prospective nonrandomized trial concerning the first HIV patient series receiving RAPA monotherapy after liver transplantation (LT).
Since June 2003, 14 HIV patients have received cadaveric donor LT due to end-stage liver disease (ESLD) associated or not associated with hepatocellular carcinoma, scored by the model for ESLD system. Patients were assessed using the following criteria for HIV characterization: CD4 T-cell count more than 100/mL and HIV-RNA levels less than 50 copies/mL. Primary immunosuppression was based on calcineurin inhibitors (CI), whereas switch to RAPA monotherapy occurred in cases of CI complications or Kaposi's sarcoma.
Mean overall post-LT follow-up was 14.8 months (range: 0.5-52.6). Six of 14 patients were administered RAPA monotherapy. Mean preswitch period from CI to RAPA was 67 days (range: 10-225 days). Mean postswitch follow-up was 11.9 months (range: 2-31 months). All patients were affected by ESLD, which was associated with hepatocellular carcinoma in seven patients. ESLD occurred due to hepatitis C virus (HCV)-related hepatopathy for nine patients, hepatitis B virus-related hepatopathy for one patient, and hepatitis B virus-HCV hepatopathy for four patients. Significantly better control of HIV and HCV replication was found among patients taking RAPA monotherapy (P=0.0001 and 0.03, respectively).
After in vitro and in vivo experimental evidence of RAPA antiviral proprieties, to our knowledge, this is the first clinical report of several significant benefits in long-term immunosuppression maintenance and HIV-1 control among HIV positive patients who underwent LT.
一些实验性试验表明，雷帕霉素（RAPA）能够通过三种不同的方式抑制 HIV-1 的进展：（1）降低 CCR5 基因转录，（2）阻断白细胞介素-2 细胞内第二信使（雷帕霉素的哺乳动物靶标），以及（3）上调β-趋化因子巨噬细胞炎症蛋白（MIP；MIP-1alpha 和 MIP-1beta）。我们提出了一项前瞻性非随机试验的初步结果，该试验涉及第一组接受 RAPA 单药治疗的 HIV 患者，这些患者在肝移植（LT）后接受了 RAPA 单药治疗。
自 2003 年 6 月以来，14 名因终末期肝病（ESLD）而接受尸体供体 LT 的 HIV 患者，因 ESLD 而评分，评分模型为 ESLD 系统。对 HIV 特征进行了以下标准评估：CD4 T 细胞计数大于 100/mL，HIV-RNA 水平小于 50 拷贝/mL。原发性免疫抑制基于钙调神经磷酸酶抑制剂（CI），而在发生 CI 并发症或卡波西肉瘤时，切换为 RAPA 单药治疗。
LT 后总体平均随访时间为 14.8 个月（范围：0.5-52.6）。14 名患者中有 6 名接受了 RAPA 单药治疗。从 CI 切换到 RAPA 的平均预切换期为 67 天（范围：10-225 天）。切换后的平均随访时间为 11.9 个月（范围：2-31 个月）。所有患者均患有 ESLD，其中 7 例伴有肝细胞癌。ESLD 由 9 例丙型肝炎病毒（HCV）相关肝病、1 例乙型肝炎病毒相关肝病和 4 例乙型肝炎病毒-HCV 肝病史引起。接受 RAPA 单药治疗的患者 HIV 和 HCV 复制的控制明显更好（分别为 P=0.0001 和 0.03）。
在体外和体内实验证明 RAPA 具有抗病毒特性之后，据我们所知，这是第一项关于接受 LT 的 HIV 阳性患者在长期免疫抑制维持和 HIV-1 控制方面具有多项显著益处的临床报告。
