Switch from TDF to TAF does not affect viral suppression in chronic HBV

In virologically suppressed patients with chronic hepatitis B virus (HBV) infection, switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) did not affect their rates of viral suppression, according to the final 96-week analysis of a phase III study.

“In chronic HBV patients on long-term TDF treatment, viral suppression was maintained, ALT* normalization increased, and bone and renal safety parameters were improved at week 96,” presented Associate Professor Pietro Lampertico from the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università di Milano, Milan, Italy, at ILC 2020.

Participants in this double-blind trial were 488 patients (mean age 51 years) with chronic HBV who had been treated with TDF (300 mg QD) for ≥48 weeks and had HBV DNA below the lower level of quantification (LLOQ) for ≥12 weeks and <20 IU/mL at screening. They were randomized 1:1 to receive TAF (25 mg QD) or TDF (300 mg QD) for 48 weeks. At week 48, all patients received open-label TAF (25 mg QD) for another 48 weeks. Patients were primarily male, Asian, and HBeAg-negative. Median duration of TDF use pre-study was >4 years, and many patients had received other HBV treatments prior to TDF.

Ninety-seven percent of patients (n=472) completed the double-blind phase, while 95 percent (n=465) completed the entire 96-week period.

At week 96, virologic suppression (HBV DNA <20 IU/mL) rate was comparable between those who received TAF in both phases (TAF-TAF) and those who received TDF during the double-blind phase followed by open-label TAF (TDF-TAF; 95 percent vs 94 percent; difference: 0.0 percent, 95 percent confidence interval, -1.9 to 1.9 percent; p=0.995). [ILC 2020, abstract AS091]

In each group, 0.4 percent of patients experienced virological failure (HBV DNA ≥20 IU/mL). No resistance was noted through the 96 weeks of treatment in the two patients who qualified for resistance testing. 

Increases in ALT normalization rates were noted in both TAF-TAF and TDF-TAF groups at week 96, though higher with TDF-TAF (74 percent vs 56 percent; p=0.051). Thirty-six and 20 patients in the TAF-TAF and TDF-TAF groups, respectively, had ALT levels above the upper limit of normal (ULN) at week 96.

There was no significant difference between TAF-TAF and TDF-TAF groups in terms of HBeAg loss (18 percent vs 9 percent; p=0.10) or seroconversion (5 percent vs 3 percent; p=0.42) or HBsAg loss (2 percent each; p=0.54) or seroconversion (<1 percent each; p=0.58).

Safety outcomes

Adverse event (AE) rates between weeks 48 and 96 were similar between TAF-TAF and TDF-TAF groups (34 percent vs 35 percent), as were grade 3–4 AEs (3 percent each) and serious AEs (3 percent vs 2 percent). None of the grade 3–4 or serious AEs were considered related to study drug. One TAF-TAF recipient discontinued treatment due to AEs. Two and one patient in the TAF-TAF and TDF-TAF groups, respectively, developed hepatocellular carcinoma. Grade 3–4 laboratory abnormality rates were numerically higher in the TDF-TAF than TAF-TAF group (12 percent vs 5 percent).

“Switching to TAF did not adversely affect metabolic profile through 96 weeks,” noted Lampertico. There was no change in the total cholesterol:HDL** cholesterol ratio at week 96 “which is a very important predictor of cardiovascular risk,” he said.

Creatinine clearance was increased at week 48 (median change from baseline 2.2 [TAF-TAF] vs -1.7 [TDF-TAF]; p<0.0001) and was sustained at week 96 (median 1.5 vs 0.5; p=0.78). There was also a sustained improvement in urinary β2-microglobulin:creatinine ratio, a marker of tubular damage, in the TAF-TAF group, and an improvement in the TDF-TAF group from week 48.

Both groups experienced changes in spine BMD***, with no significant difference between the TAF-TAF and TDF-TAF groups (mean change 2.33 percent vs 1.73 percent; p=0.097). However, there was a greater increase in hip BMD in the TAF-TAF than TDF-TAF group (mean change 1.16 percent vs 0.18 percent; p<0.001). Twenty-one and 38 percent of patients improved from osteoporosis to osteopenia of the spine and hip, respectively, while ≤3 percent experienced a negative T-score shift.