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.

First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation / Di Benedetto, F; Di Sandro, S; De Ruvo, N; Montalti, R; Ballarin, R; Guerrini, GP; Spaggiari, M; Guaraldi, G; Gerunda, G. - In: TRANSPLANTATION. - ISSN 0041-1337. - STAMPA. - 89:6(2010), pp. 733-738. [10.1097/TP.0b013e3181c7dcc0]

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

Di Benedetto F;Di Sandro S;Ballarin R;Guerrini GP;Spaggiari M;Guaraldi G;Gerunda G
2010

Abstract

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.
89
6
733
738
First report on a series of HIV patients undergoing rapamycin monotherapy after liver transplantation / Di Benedetto, F; Di Sandro, S; De Ruvo, N; Montalti, R; Ballarin, R; Guerrini, GP; Spaggiari, M; Guaraldi, G; Gerunda, G. - In: TRANSPLANTATION. - ISSN 0041-1337. - STAMPA. - 89:6(2010), pp. 733-738. [10.1097/TP.0b013e3181c7dcc0]
Di Benedetto, F; Di Sandro, S; De Ruvo, N; Montalti, R; Ballarin, R; Guerrini, Gp; Spaggiari, M; Guaraldi, G; Gerunda, G
File in questo prodotto:
File Dimensione Formato  
19.pdf

non disponibili

Tipologia: Post-print dell'autore (bozza post referaggio)
Dimensione 342 kB
Formato Adobe PDF
342 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1202138
Citazioni
  • ???jsp.display-item.citation.pmc??? 27
  • Scopus 54
  • ???jsp.display-item.citation.isi??? 54
social impact