Early hepatitis B virological rebound on entecavir through selection of lamivudine-associated mutations.

G109A in the reverse transcriptase region, and I13V, L33I, L63P and V77I in the protease region. The last HAART regimen before transplantation, discontinued pre-operatively, was lamivudine 150 mg twice a day, tenofovir 300 mg once daily and fosampre-navir 1400 mg twice a day. Immunosuppression was initially achieved with cyclosporin (300 mg twice a day) and steroids, and then maintained with cyclosporin only. On the third post-operative day, HAART was resumed with emtricitabine 200 mg, tenofovir 300 mg once daily and a subcutaneous (sc) injection of enfuvirtide 90 mg twice a day. At 3 months after transplantation, the CD4þ T cell count and HIV RNA level were 263 cells/mm 3 (20%) and ,50 copies/mL, respectively, while HCV RNA was 4.09 log 10 copies/mL (Cobas Ampliprep/Cobas TaqMan HCV Test Roche Diagnostics). After 9 months, because of a further increase in HCV RNA levels (6.09 log 10 copies/mL) and of macro-and micronodular cirrhosis revealed by transjugular liver biopsy, the patient started anti-HCV treatment with pegylated interferon (PEG-IFN) alfa 2b (180 mg sc once a week) and riba-virin (1200 mg twice a day). Cyclosporin was administered twice daily and its dosage was adjusted individually to match target trough levels of 75– 125 mg/L. Four weeks later, because he had ongoing injection site reactions and complained of injection fatigue due to enfuvirtide and PEG-IFN, the patient switched from enfuvirtide to raltegravir (400 mg twice a day). Four weeks later, HIV RNA was still ,50 copies/mL, while the CD4þ T cell count had increased from 162 (18%) to 336 (23%). Self-reported therapeutic adherence was apparently optimal. No other potentially interacting drugs were administered. Cyclosporin levels were monitored at regular intervals during outpatient visits (Figure 1). Moreover, at week 4 and week 8 raltegravir concentrations were also measured by a validated HPLC method 7 before the morning dose and 3 h later and showed drug levels to be 60 and 5165 ng/mL at week 4, and 119 and 3386 ng/mL at week 8, respectively. No specific toxicity related to antiretroviral and immunosuppressive therapies was recorded. No administration of factor VIII for treatment of haemophilia A was requested. After 18 months of follow-up post-transplantation, the patient is alive and HIV RNA levels are undetectable. In our patient, a raltegravir-based regimen was chosen in order to avoid the potential deleterious effect of PIs on cyclos-porin. A new NNRTI-based regimen was excluded because etra-virine is a substrate for, and inhibitor …