Substituting tenofovir alafenamide for tenofovir disoproxil fumarate in virologically suppressed patients with chronic hepatitis B virus (HBV) infection can be done for improved safety with no loss in efficacy, according to data published in the Lancet Gastroenterology & Hepatology.
In this noninferiority study, patients with HBV who had been receiving tenofovir disoproxil fumarate for 48 weeks or more and who had HBV DNA less than the lower limit of quantification for at least 12 weeks were recruited. Patients were randomly assigned to either switch to receiving tenofovir alafenamide 25 mg once a day (n=243) or to continue receiving tenofovir disoproxil fumarate 300 mg once a day (n=245).
At week 48, 1 patient from each group had HBV DNA of at least 20 IU/mL (difference in proportion, 0.0%, 95% CI, −1.9 to 2.0), indicating noninferior efficacy of tenofovir alafenamide to tenofovir disoproxil fumarate.
At week 48, patients receiving tenofovir alafenamide also had significantly increased bone mineral density at hip (mean change, 0.66% vs −0.51%; difference in least square means, 1.17%; 95% CI, 0.80-1.54; P <.0001) and at spine (mean change, 1.74% vs −0.11%).
Upper respiratory tract infections occurred in 7% of patients in each group and, along with nasopharyngitis, which occurred in 5% of patients in each group, were the most common treatment-emergent adverse events. In both groups, the incidence of grade 3 and above adverse events was low, and no viral resistance was observed in patients who qualified for viral sequencing.
According to investigators, although the sample sizes were sufficient to assess noninferiority in efficacy, the 48-week duration might not be long enough to reflect potential long-term differences in switching drugs. However, follow-up of patients during the 48-week open-label tenofovir alafenamide extension phase is ongoing.
Another limitation of this work is the enrollment of patients with estimated glomerular ﬁltration rate of at least 50 mL/min only, limiting the generalization of the results to the population at large.
It was also noted that the study is ongoing, and further results will be published later. Finally, patients with decompensated cirrhosis (Child-Pugh-Turcotte B or C) and those with moderate or severe renal impairment, including those with end-stage renal disease receiving hemodialysis, were not assessed. Again, further studies with these important patient populations are ongoing.
The investigators concluded that “in virally suppressed patients with chronic HBV infection receiving long-term tenofovir disoproxil fumarate treatment, we have shown that switching to tenofovir alafenamide is safe and effective, and that tenofovir disoproxil fumarate-associated renal and bone abnormalities are improved on switching to tenofovir alafenamide.” However, although the short-term benefits are promising, the potential clinical benefits of switching will require confirmation in longer term follow-up studies.
Disclosure: This study was funded by Gilead Sciences. Please refer to original reference for a full list of author disclosures.
Lampertico P, Buti M, Fung S, et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patients with chronic hepatitis B: a randomised, double-blind, phase 3, multicentre non-inferiority study [published online February 20, 2020]. Lancet Gastroenterol Hepatol. doi:10.1016/S2468-1253(19)30421-2.