First Report on a Series of HIV Patients Undergoing Rapamycin Monotherapy After Liver Transplantation

• DOI: 10.1097/tp.0b013e3181c7dcc0
• Publication Date: 2010-03-15T18:49:21Z
• Authors: Fabrizio Di Bened...; Stefano Di Sandro; Nicola De Ruvo; Roberto Montalti; Roberto Ballarin; Gian Piero Guerrini; Mario Spaggiari; Giovanni Guaraldi; Giorgio Gerunda
• Keywords: Adult; Graft Rejection; Male; Hepatitis B virus; Time Factors; Anti-HIV Agents; Antiretroviral Therapy; HIV Infections; Hepacivirus; Kaplan-Meier Estimate; 03 medical and health sciences; 0302 clinical medicine; Antiretroviral Therapy, Highly Active; Humans; Highly Active; Viral; Prospective Studies; Sirolimus; Graft Survival; Adult, Anti-HIV Agents; therapeutic use, Antiretroviral Therapy; Highly Active, CD4 Lymphocyte Count, Female, Graft Rejection; etiology/prevention /&/ control, Graft Survival, HIV Infections; complications/drug therapy/immunology/mortality/virology, HIV-1; drug effects/genetics/growth /&/ development, Hepacivirus; genetics, Hepatitis B virus; genetics, Hepatitis B; complications/diagnosis/mortality/surgery, Hepatitis C; complications/diagnosis/mortality/surgery, Humans, Immunosuppressive Agents; adverse effects/therapeutic use, Kaplan-Meier Estimate, Liver Transplantation; adverse effects, Male, Middle Aged, Prospective Studies, RNA; Viral; blood, Sirolimus; adverse effects/therapeutic use, Time Factors, Treatment Outcome, Viral Load; Viral Load; Middle Aged; Hepatitis B; Hepatitis C; CD4 Lymphocyte Count; Liver Transplantation; 3. Good health; Treatment Outcome; HIV-1; Adult; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; Graft Rejection; Graft Survival; HIV Infections; HIV-1; Hepacivirus; Hepatitis B; Hepatitis B virus; Hepatitis C; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Prospective Studies; RNA, Viral; Sirolimus; Time Factors; Treatment Outcome; Viral Load; Liver Transplantation; RNA; Female; Immunosuppressive Agents

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.