1. First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation
- Author
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Roberto Ballarin, Roberto Montalti, Gian Piero Guerrini, Nicola De Ruvo, Stefano Di Sandro, Giorgio Enrico Gerunda, Giovanni Guaraldi, Mario Spaggiari, Fabrizio Di Benedetto, Di Benedetto, Fabrizio, Di Sandro, Stefano, De Ruvo, Nicola, Montalti, Roberto, Ballarin, Roberto, Guerrini, Gian Piero, Spaggiari, Mario, Guaraldi, Giovanni, and Gerunda, Giorgio
- Subjects
Graft Rejection ,Male ,Time Factors ,medicine.medical_treatment ,HIV Infections ,Hepacivirus ,Kaplan-Meier Estimate ,Liver transplantation ,Gastroenterology ,complications/drug therapy/immunology/mortality/virology ,Immunosuppressive Agent ,Liver disease ,Antiretroviral Therapy, Highly Active ,genetics ,HIV Infection ,Sirolimu ,Viral ,Prospective Studies ,Graft Survival ,etiology/prevention /& ,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 ,blood, Sirolimus ,adverse effects/therapeutic use, Time Factors, Treatment Outcome, Viral Load ,Immunosuppression ,Hepatitis B viru ,Hepatitis C ,Hepatitis B ,Middle Aged ,Viral Load ,adverse effects/therapeutic use ,Treatment Outcome ,Hepatocellular carcinoma ,RNA, Viral ,Female ,development ,Viral load ,Immunosuppressive Agents ,Human ,Adult ,medicine.medical_specialty ,Hepatitis B virus ,Time Factor ,Anti-HIV Agents ,Antiretroviral Therapy ,complications/diagnosis/mortality/surgery ,drug effects/genetics/growth /& ,blood ,Internal medicine ,medicine ,Humans ,Highly Active ,Sirolimus ,Transplantation ,Hepaciviru ,control ,business.industry ,Anti-HIV Agent ,medicine.disease ,CD4 Lymphocyte Count ,Liver Transplantation ,Prospective Studie ,therapeutic use ,Immunology ,adverse effects ,HIV-1 ,RNA ,business - Abstract
INTRODUCTION: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
- Published
- 2010