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Published on: August 27, 2019
First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation
Fabrizio Di Benedetto1, Stefano Di Sandro, Nicola De Ruvo
1Liver and Multivisceral Transplant Center, University of Modena and Reggio Emilia, Modena, Italy. f.diben@virgilio.it
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.
Insights
Rapamycin (RAPA) monotherapy shows promise in controlling HIV-1 and Hepatitis C virus (HCV) in liver transplant patients. This study highlights RAPA
Area of Science:
- Immunology
- Virology
- Hepatology
Background:
- Rapamycin (RAPA) demonstrates potential in inhibiting HIV-1 progression through multiple mechanisms.
- Experimental data suggests RAPA's antiviral properties.
- This study investigates RAPA's efficacy in HIV patients post-liver transplantation (LT).
Purpose of the Study:
- To evaluate the preliminary results of RAPA monotherapy in HIV patients after LT.
- To assess the impact of RAPA on HIV-1 and HCV control in this patient cohort.
Main Methods:
- Prospective, nonrandomized trial involving 14 HIV patients undergoing LT.
- Patients received calcineurin inhibitors (CI) primarily, switching to RAPA monotherapy if complications arose.
- HIV characterization included CD4 T-cell count and HIV-RNA levels.
Main Results:
- Six out of 14 patients received RAPA monotherapy.
- Patients on RAPA monotherapy showed significantly better control of HIV and HCV replication (P=0.0001 and 0.03, respectively).
- Mean post-LT follow-up was 14.8 months.
Conclusions:
- This is the first clinical report on RAPA's benefits in long-term immunosuppression and HIV-1 control post-LT.
- RAPA monotherapy appears to offer significant advantages for HIV-positive patients undergoing liver transplantation.
- Further research is warranted to confirm these findings.
