First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation

Transplantation. 2010 Mar 27;89(6):733-8. doi: 10.1097/TP.0b013e3181c7dcc0.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Female
  • Graft Rejection / etiology
  • Graft Rejection / prevention & control
  • Graft Survival
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / mortality
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / growth & development
  • Hepacivirus / genetics
  • Hepatitis B / complications
  • Hepatitis B / diagnosis
  • Hepatitis B / mortality
  • Hepatitis B / surgery*
  • Hepatitis B virus / genetics
  • Hepatitis C / complications
  • Hepatitis C / diagnosis
  • Hepatitis C / mortality
  • Hepatitis C / surgery*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Liver Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Viral / blood
  • Sirolimus / adverse effects
  • Sirolimus / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents
  • Immunosuppressive Agents
  • RNA, Viral
  • Sirolimus