In an open-label, phase 2 study, tenofovir alafenamide (TAF) monotherapy exhibited non-inferior efficacy and improved safety profiles compared with tenofovir disoproxil fumarate (TDF).¹ The study investigated the long-term bone and renal safety of TAF compared with TDF in pretransplant diagnosis of hepatitis B virus (HBV) and chronic kidney disease (CKD) patients, with parameters including changes with serum creatinine (SCr), markers of tubular proteinuria, spine and hip bone mineral density (BMD), and bone-related biomarkers (BBMs).¹ The long-term efficacy and safety results of the 192 weeks showed the benefits and supported the switching from TDF regimens to TAF therapy for chronic HBV patients.¹

Orthotopic liver transplantation (OLT) in chronic HBV-infected recipients was associated with viral recurrence and poor survival rates, leading to the development of comorbidities, such as CKD and post-OLT complications including nephrotoxicity from calcineurin inhibitor use and osteoporosis.^1-3 Novel tenofovir prodrug TAF, like TDF, a current standard of care for chronic HBV infection, is an antiretroviral agent used for the prophylaxis of HBV relapse.¹ Compared with TDF, TAF enhances plasma stability, uptake by lymphoid tissue, and hepatic delivery of active drug while observing reduced circulating tenofovir level, hence treatment using TAF is associated with better kidney and bone safety.^1,4

The study was conducted to evaluate the long-term renal and bone safety of TAF, compared with TDF enrolled patients who were diagnosed to have chronic HBV infection prior to OLT maintained on TDF alone or a TDF-containing regimen and underwent OLT ³12 weeks prior to screening.¹ The trial included 2 phases: the randomized phase and the open-label extension (OLE) phase.¹ The randomized phase lasted for 48 weeks, during which enrolled patients were randomized 1:1 into 2 groups to receive TAF 25mg daily (the TAF group) or continued their TDF-containing regimen (the TDF-to-TAF group).¹ After 48 weeks, both groups entered into the OLE phase to receive TAF 25mg once daily for another 144 weeks until week 192.¹

Renal functions of patients were assessed by changes in the estimated glomerular filtration rate (eGFR) obtained through creatinine- and non-creatinine-based equations using data of changes with SCr.¹ Patients who received the TAF treatment during the randomized phase had improved eGFR, which remained stable through the entire trial.¹ The eGFR values had a generally more significant improvement in the TAF group than the TDF-to-TAF group, and the difference was most notable with the eGFR_{CKD-EPI cystatin C} values, recording the changes of +4.2 and -4.5mL/min/1.73m² for each group, respectively.¹ The safety of TAF was supported by stable or improved CKD stages in all patients with CKD stage II or III at baseline throughout the study, and with similar changes in the renal proximal tubular markers in both study groups.¹

The parameters of bone safety included changes in spine and hip BMD, as well as serum markers of bone turnover, and both parameters saw improvements after the TAF treatment.¹ The median spine BMD changes from baseline were consistent, i.e., +1.5% at week 48 to +1.6% at week 192 for the TAF group; and a significant improvement was observed in the TDF-to-TAF group following the change of regimen, i.e., from -1.0% at week 48 to +2.4% at week 192.¹ Regardless of the baseline renal function, patients in the TAF group showed similar improvements in BMD of both spine and hip, while patients receiving TDF with baseline eGFR_CKD-EPI <50mL/min/1.73m² had notably larger drops in BMD, proving that TAF is a better regimen for patients with a more compromised renal function.¹ The bone biomarkers c-type collagen sequence and procollagen type I N-terminal propeptide (PINP) showed no significant difference in change from baseline for both groups.¹

In conclusion, TAF was shown to be non-inferior in efficacy and superior in safety compared with TDF.¹ While the TDF usage increases the risk of renal impairment and BMD loss, TAF is able to maintain a continued renal and bone safety profile, regardless of the baseline renal function of patients.^1,5 Thus, switching from TDF-containing regimens to TAF therapy can be much safer to the post-OLT patient outcomes, while keeping high antiviral efficacy against HBV relapse.^1,6