Tenofovir alafenamide may safely replace tenofovir disoproxil fumarate in patients with drug-resistant HBV, trial finds

An industry-funded randomized trial found that tenofovir alafenamide could be substituted for tenofovir disoproxil fumarate in patients with multidrug-resistant hepatitis B virus (HBV) for improved bone and renal safety without a loss of efficacy; however, the former drug was associated with greater increases in body weight and cholesterol levels.

Tenofovir alafenamide (TAF) may be a safe substitute for tenofovir disoproxil fumarate (TDF) in patients with drug-resistant hepatitis B virus (HBV), a trial found.

Researchers randomized 174 patients who had HBV resistant to multiple drugs (lamivudine, entecavir, and/or adefovir) and had been taking TDF monotherapy for 96 weeks or longer to switch to TAF (n=87) or to continue TDF (n=87) for 48 weeks. The primary end point was the proportion of patients with HBV DNA less than 60 IU/mL at week 48. The study was financially supported by Gilead Sciences, which also provided the study drugs. Results were published online on May 4 by Clinical Gastroenterology and Hepatology.

At baseline, 84 and 80 patients had HBV DNA less than 60 IU/mL in the TAF and TDF groups, respectively. At week 48, the proportion of patients with HBV DNA less than 60 IU/mL was 98.9% (86 of 87) in the TAF group, showing noninferiority to the TDF group (97.7%; 85 of 87; difference, 1.1% [95% CI, −2.7% to 5.0%]). The change in median alanine aminotransferase level at week 48 from baseline was also different between groups (−3 IU/L in the TAF group vs. 2 IU/L in the TDF group; P=0.02). In addition, the TAF group showed a statistically greater increase in bone mineral density at spine (1.84% vs. 0.08%; P=0.01) and a numerically higher increase in mean estimated glomerular filtration rate (8.2% vs. 4.5%; P=0.06) compared with the TDF group.

Patients in the TAF group, compared to those in the TDF group, had significantly greater increases in mean body weight (0.71 vs. −0.37 kg; P=0.01) and total, low-density lipoprotein, and high-density lipoprotein cholesterol levels (P<0.001 for all) at week 48 from baseline. The TDF group had significantly more frequent serious adverse events than the TAF group (12 [13.8%] vs. 2 [2.3%]; P=0.01). Overall, of the 108 HBeAg-positive patients at baseline, the rate of HBeAg seroclearance was not significantly different between the TAF and TDF groups (9.6% [5 of 52] vs. 14.3% [8 of 56]; P=0.65). One patient in the TAF group, and none in the TDF group, achieved HBsAg seroclearance at week 48.

The trial was limited by its open-label design and the fact that all participants had genotype C HBV, the authors noted. They added that the trial's treatment duration was relatively short and that a longer follow-up assessment would be warranted to evaluate the safety and efficacy of switching from TDF to TAF in patients with drug-resistant HBV.

“Considering the necessity of long-term antiviral therapy to maintain viral suppression particularly in the patients with drug-resistant HBV due to low rate of serologic responses, our data may provide novel insights in the selection of the treatment,” the authors concluded. “Future long-term research would be required to investigate the impact of these complex safety signals with TAF treatment on clinical outcomes of the patients with [chronic hepatitis B].”