January 18, 2018
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Tenofovir alafenamide effectively treats HBV, no virologic resistance

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Treatment with tenofovir alafenamide was as effective in suppressing hepatitis B replication as tenofovir disoproxil fumarate with no virologic resistance, according to recently published data on two 96-week trials.

“Tenofovir alafenamide (TAF) is an orally bioavailable prodrug of tenofovir (TFV), a nucleotide analog that inhibits reverse transcription of HIV and HBV,” Kosh Agarwal, MD, from Kings College Hospital, United Kingdom, and colleagues wrote. “TAF was designed to have greater plasma stability than tenofovir disoproxil fumarate (TDF) allowing delivery of the active metabolite, tenofovir diphosphate, to hepatocytes more efficiently than TDF, which must be dosed at relatively high levels to achieve a therapeutic concentration in hepatic cells.”

Study GS-US-320-0110 included 792 patients who were positive for hepatitis B e-antigen and completed 96 weeks of treatment with either TAF 25 mg (n = 530) or TDF 300 mg (n = 262). Study GS-US-320-0108 included 395 patients who were negative for HBeAg and completed 96 weeks of treatment with either TAF (n = 266) or TDF (n = 129). The randomized, double-blind studies were identical in design.

HBeAg-positive study

At the end of 96 weeks, the proportion of patients who received TAF and had HBV DNA less than 29 IU/mL was 73% compared with 75% in those treated with TDF. The adjusted difference of –2.2% (95% CI, –8.3% to 3.9%) was not significant.

The researchers observed treatment failure — or remaining HBV DNA of 29 IU/mL or higher — in 14% of patients treated with TDF and 18% of patients treated with TAF.

The proportion of patients with alanine aminotransferase above the upper limit of normal at baseline who achieved normal ALT at week 96 was 75% in patients who received TAF and 68% in those who received TDF, which researchers reported was significant (8%; 95% CI, 1.2-14.7).

The rate of HBeAg loss between the two groups was 22% in patients who received TAF compared with 18% among those who received TDF. Additionally, the rate of HBeAg seroconversion was 18% in the TAF group compared with 12% in the TDF group. The data indicated neither sets of rates were significantly different.

HBeAg-negative study

At study end, the proportion of patients negative for HBeAg who received TAF and had HBV DNA less than 29 IU/mL was 90% compared with 91% in those treated with TDF. The adjusted difference of –0.6% (95% CI, –7% to 5.8%) was not significant.

The researchers observed treatment failure in 41 patients at week 96, eight of whom had verified HBV DNA of 29 IU/mL or higher between the TAF group (n = 5) and TDF group (n = 3).

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The researchers observed treatment failure — or remaining HBV DNA of 29 IU/mL or higher — in 14% of patients treated with TDF and 18% of patients treated with TAF.

The proportion of patients with ALT above the upper limit of normal at baseline who achieved normal ALT at week 96 was 81% in patients who received TAF and 71% in those who received TDF, the difference of which was significant (9.8%; 95% CI, 0.2-19.3).

One HBeAg-negative patient treated with TAF experienced loss of HBV surface antigen and achieved seroconversion to anti-HBs. The researchers observed small but similar mean declines in HBsAg levels in both the TAF group (–0.14) and TDF group (–0.1).

“Consistent with week 48 results, treatment effects between TAF and TDF did not differ statistically in prespecified subgroups including age, race, region, HBV genotype, baseline HBV DNA level and prior oral antiviral treatment status,” the researchers wrote. “Through 96 weeks of double-blind treatment, no resistance development was seen in either treatment group. Further, the superior safety profile of TAF relative to TDF with regard to bone and renal parameters seen at week 48 is confirmed through 96 weeks of double-blind treatment.” – by Talitha Bennett

Disclosure: Agarwal reports he received advisory board, speaker and consultant fees from AbbVie, Achillion, BMS, GSK, Gilead, Intercept, Janssen, Merck, Novartis and Roche; and grants from BMS, Gilead and Roche. Please see the full study for the other authors’ relevant financial disclosures.