TAF rivals TDF for CHB suppression after orthotopic liver transplantation

Switching from tenofovir disoproxil fumarate (TDF) regimens to tenofovir alafenamide (TAF) monotherapy demonstrates long-term efficacy and safety in orthotopic liver transplantation (OLT) recipients with chronic hepatitis B virus (HBV) infection, reports a study presented at The Liver Meeting Digital Experience 2021, by the American Association for the Study of Liver Diseases (AASLD 2021).

In particular, TAF maintains viral suppression through 4 years of follow-up while also yielding notable improvements in bone and renal parameters.

The researchers conducted an open-label, phase II study, enrolling 51 OLT recipients who were first randomized to receive either TAF or a TDF-containing regimen for 48 weeks. This was followed by an open-label extension (OLE) phase where all patients received only TAF monotherapy at 25-mg, once-daily doses through week 192.

The primary efficacy endpoint was viral suppression, defined as HBV DNA levels <20 IU/mL. Safety outcomes included serious adverse events (AE) as well as changes in estimated glomerular filtration rate (eGFR) and bone mineral density (BMD) at the hip and spine. All were evaluated after week 192.

By the end of the study, five participants prematurely discontinued medication, two dropped out due to AEs, one withdrew consent, and two died. Further excluding those with missing data, 20 patients each in the TAF and TDF arms remained available for analysis, all of whom showed sustained viral suppression through 192 weeks of treatment. [AASLD 2021, abstract 803]

In addition, one participant in the TAF arm showed loss or seroconversion of the HB e antigen, though no such outcome in either group was reported for the HB surface antigen.

Switching to TAF also showed comparable safety to the TDF regimens. In the randomized phase, 92 percent and 96 percent of patients in the TAF and TDF arms developed any AE, respectively. In OLE, all TDF patients who switched to TAF developed AEs. Grade 3–4 and serious AEs were also common, occurring in 23 percent to 33 percent of patients during the OLE phase.

Notably, the researchers saw that aside from having a comparable safety and efficacy profile to TDF regimens, TAF also led to improvements in eGFR during the randomized phase, which remained stable during OLE. Patients who were initially on TDF and switched to TAF also saw stable eGFR without notable deteriorations during OLE.

Similarly, during the randomized phase, patients on TAF saw better hip and spine BMD relative to TDF-containing regimens. During OLE, patients switched from TDF to TAF showed BMD improvements through week 192.

“The favourable effects of TAF in maintaining viral suppression and improved bone and renal safety profile relative to TDF lend support for the use of TAF in patients with chronic HBV who are post-OLT,” the researchers said.