Long-term TAF tied to high viral suppression in CHB

Patients with chronic hepatitis B (CHB) who has undergone long-term treatment with tenofovir alafenamide (TAF) achieve high rates of viral suppression comparable to those of tenofovir disoproxil fumarate (TDF; or TDF switched to TAF) with favourable renal and bone safety, results of a study have shown.

“These findings, coupled with the absence of documented resistance, provide continued support for TAF as a preferred treatment for CHB infection,” said the researchers led by Dr Henry LY Chan, Chinese University of Hong Kong, People's Republic of China.

Chan and his team randomly assigned 1,298 patients with HBeAg-negative or -positive CHB with or without compensated cirrhosis to receive either TAF 25 mg or TDF 300 mg once daily for up to 3 years, followed by open-label TAF for up to 8 years.

Pooled analyses were also carried out to assess efficacy (antiviral, biochemical, and serologic), resistance (deep sequencing of polymerase/reverse transcriptase and phenotyping), and safety, including renal and bone parameters.

Of the patients, 866 received TAF in the double-blind and open-label phases, while 432 received TDF who then switched to TAF at year 2 (n=180; TDF→TAF3y) or year 3 (n=202; TDF→TAF2y). Fifty patients (4 percent) on TDF discontinued treatment and were then excluded from the analysis. [Am J Gastroenterol 2024;119:486-496]

At year 5, 85 percent of patients in the TAF arm, 83 percent in the TDF→TAF3y arm, and 90 percent in the TDF→TAF2y arm achieved HBV DNA <29 IU/mL (missing=failure). None of them developed resistance to either treatment.

Bone density

Using Cockcroft-Gault, the median estimated glomerular filtration rate decreased by <2.5 mL/min. Mean reductions of <1 percent in hip and spine bone mineral density occurred at year 5 in the TAF arm, while patients who rolled over to TAF from TDF showed improvements in these parameters at year 5 following the switch.

“Building on previous published results from these two large phase III studies, 5-year findings show continued high rates of viral suppression among those randomized to receive TAF and among those randomized to receive TDF who were subsequently switched to TAF for the open-label phase,” Chan said. [Lancet Gastroenterol Hepatol 2016;1:196-206; J Hepatol 2018;68:672-681]

“Importantly, the improved bone and renal safety parameters initially reported with TAF were maintained through 5 years, and no resistance has been identified to date,” he added. [Lancet Gastroenterol Hepatol 2016;1:185-195; Antimicrob Agents Chemother 2018;62:e01064-1068]

These findings were consistent with real-world evidence up to 144 weeks among patients who switched to TAF. [Aliment Pharmacol Ther 2022;56:713-722]

Nearly 296 million people are affected by hepatitis B virus (HBV) infection across the globe. HBV infection, if not managed properly, may lead to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. [Lancet Gastroenterol Hepatol 2018;3:383-403; Lancet 2018;392:2313-2324; https://www.who.int/en/news-room/fact-sheets/detail/hepatitis-b]

“As the CHB population ages, associated comorbidities, such as renal and bone diseases, highlight the need for optimization of anti-HBV therapies,” according to Chan and colleagues.