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We designed a randomized trial to assess whether the early withdrawal of cyclosporine (CsA) followed by the initiation of everolimus (Evr) monotherapy in de novoliver transplantation (LT) patients would result in superior renal function compared to a CsA‐based immunosuppression protocol. All patients were treated with CsA for the first 10 days and then randomized to receive Evr in combination with CsA up to day 30, then either continued on Evr monotherapy (Evr group) or maintained on CsA with/without mycophenolate mofetil (CsA group) in case of chronic kidney disease (CKD). Seventy‐eight patients were randomized (Evr n = 52; CsA n = 26). The 1‐year freedom from efficacy failure in Evr group was 75% versus 69.2% in CsA group, p = 0.36. There was no statistically significant difference in patient survival between the two groups. Mean modification of diet in renal disease (MDRD) was significantly better in the Evr group at 12 months (87.7 ± 26.1 vs. 59.9 ± 12.6 mL/min; p < 0.001). The incidence of CKD stage ≥3 (estimated glomerular filtration rate <60 mL/min) was higher in the CsA group at 1 year (52.2% vs. 15.4%, p = 0.005). The results indicate that early withdrawal of CsA followed by Evr monotherapy in de novoLT patients is associated with an improvement in renal function, with a similar incidence of rejection and major complications.

We designed a randomized trial to assess whether the early withdrawal of cyclosporine (CsA) followed by the initiation of everolimus (Evr) monotherapy in de novoliver transplantation (LT) patients would result in superior renal function compared to a CsA‐based immunosuppression protocol. All patients were treated with CsA for the first 10 days and then randomized to receive Evr in combination with CsA up to day 30, then either continued on Evr monotherapy (Evr group) or maintained on CsA with/without mycophenolate mofetil (CsA group) in case of chronic kidney disease (CKD). Seventy‐eight patients were randomized (Evr n = 52; CsA n = 26). The 1‐year freedom from efficacy failure in Evr group was 75% versus 69.2% in CsA group, p = 0.36. There was no statistically significant difference in patient survival between the two groups. Mean modification of diet in renal disease (MDRD) was significantly better in the Evr group at 12 months (87.7 ± 26.1 vs. 59.9 ± 12.6 mL/min; p < 0.001). The incidence of CKD stage ≥3 (estimated glomerular filtration rate <60 mL/min) was higher in the CsA group at 1 year (52.2% vs. 15.4%, p = 0.005). The results indicate that early withdrawal of CsA followed by Evr monotherapy in de novoLT patients is associated with an improvement in renal function, with a similar incidence of rejection and major complications.

Pharmacokinetic (PK) interactions between protease inhibitors (PIs) and immunosuppressive agents (IS) are critical elements in the management of HIV-infected patients who undergo liver transplantation (LTx). The primary objective of this study was to evaluate the decreases in IS dosages necessary to maintain an appropriate therapeutic window (TW) after initiating PI-based antiretroviral therapy regimens post-LTx. Single-center, PK cross-sectional study of consecutive HIV-infected adult patients who underwent LTxwas done. Blood trough concentrations (Ct) of IS were obtained using a commercial MEIA test; plasma Ctof PIswere measured using HPLC. Twelve consecutive HIV-infected adult patients (11 males, 1 female) were enrolled. More rapid increases in IS plasma Ctwere observed 48 h after initiating ritonavir (RTV)-boosted PI therapy post-LTxthan when using unboosted PIs. Seven patients developed acute renal failure. The median fold decrease in IS dosages required to regain IS concentrations that were in the TW was 7.5 (range 6–14) after resuming boosted PIsand 2.9 (range 2–4) after unboosted PIs. The overall median time necessary to reach IS TW after dose adjustment was 3.5 days (range 0–15). Unboosted PIsexhibited lesser PK interactions with IS than did RTV-boosted PIsand were thus more amenable to use in the post-LTxsetting.

Pharmacokinetic (PK) interactions between protease inhibitors (PIs) and immunosuppressive agents (IS) are critical elements in the management of HIV-infected patients who undergo liver transplantation (LTx). The primary objective of this study was to evaluate the decreases in IS dosages necessary to maintain an appropriate therapeutic window (TW) after initiating PI-based antiretroviral therapy regimens post-LTx. Single-center, PK cross-sectional study of consecutive HIV-infected adult patients who underwent LTxwas done. Blood trough concentrations (Ct) of IS were obtained using a commercial MEIA test; plasma Ctof PIswere measured using HPLC. Twelve consecutive HIV-infected adult patients (11 males, 1 female) were enrolled. More rapid increases in IS plasma Ctwere observed 48 h after initiating ritonavir (RTV)-boosted PI therapy post-LTxthan when using unboosted PIs. Seven patients developed acute renal failure. The median fold decrease in IS dosages required to regain IS concentrations that were in the TW was 7.5 (range 6-14) after resuming boosted PIsand 2.9 (range 2-4) after unboosted PIs. The overall median time necessary to reach IS TW after dose adjustment was 3.5 days (range 0-15). Unboosted PIsexhibited lesser PK interactions with IS than did RTV-boosted PIsand were thus more amenable to use in the post-LTxsetting.

The unique phenomenon of human herpesvirus-6 (HHV-6) chromosomal integration (CIHHV-6) may account for clinical drawbacks in transplant setting, being misinterpreted as active infection and leading to unnecessary and potentially harmful treatments. We have investigated the prevalence of CIHHV-6 in 205 consecutive solid organ (SO) and allogeneic stem cell transplant (alloSCT) Italian patients. Fifty-two (38.5%) of 135 solid organ transplant (SOT) and 16 (22.8%) of 70 alloSCT patients resulted positive for plasma HHV-6 DNA by real-time polymerase chain reaction. Seven SOT and three alloSCT patients presented HHV-6-related diseases, requiring antivirals. Two further patients (0.9%) were identified, presenting high HHV-6 loads. The quantification of HHV-6 on hair follicles disclosed the integrated state, allowing the discontinuation of antivirals. Before starting specific treatments, CIHHV-6 should be excluded in transplant patients with HHV-6 viremia by the comparison of HHV-6 loads on different fluids and tissues. Pretransplantation screening of donors and recipients may further prevent the misdiagnosis of CIHHV-6.

The unique phenomenon of human herpesvirus-6 (HHV-6) chromosomal integration (CIHHV-6) may account for clinical drawbacks in transplant setting, being misinterpreted as active infection and leading to unnecessary and potentially harmful treatments. We have investigated the prevalence of CIHHV-6 in 205 consecutive solid organ (SO) and allogeneic stem cell transplant (alloSCT) Italian patients. Fifty-two (38.5) of 135 solid organ transplant (SOT) and 16 (22.8) of 70 alloSCT patients resulted positive for plasma HHV-6 DNA by real-time polymerase chain reaction. Seven SOT and three alloSCT patients presented HHV-6-related diseases, requiring antivirals. Two further patients (0.9) were identified, presenting high HHV-6 loads. The quantification of HHV-6 on hair follicles disclosed the integrated state, allowing the discontinuation of antivirals. Before starting specific treatments, CIHHV-6 should be excluded in transplant patients with HHV-6 viremia by the comparison of HHV-6 loads on different fluids and tissues. Pretransplantation screening of donors and recipients may further prevent the misdiagnosis of CIHHV-6.