Long-term TDF therapy offers sustained HBV suppression without resistance

By Lucy Piper, Senior medwireNews Reporter

Patients with chronic hepatitis B virus (HBV) infection can achieve sustained viral suppression with long-term tenofovir disoproxil fumarate (TDF) treatment without developing resistance, shows a 7-year study.

For 437 patients who took TDF for 7 years, 99.3% maintained viral suppression, at an HBV DNA level below 69 IU/mL, with no resistance to the drug detected.

“The lack of resistance to TDF after prolonged exposure is striking”, say the study researchers, who observe that other nucleos(t)ide analogues have high rates of resistance, with 5-year rates ranging from 20% for adefovir dipivoxil (ADV) treatment to 65% for lamivudine treatment.

The current study involved mainly treatment-naïve patients, but there are previous reports of a lack of resistance with TDF through 2.0 and 3.5 years in lamivudine- and ADV-resistant patients.

“The absence of viral resistance to TDF carries important implications for clinical outcomes, because patients without resistance development may have a lower risk of liver disease progression”, comments the team, led by Maria Buti (Hospital General Universitari Vall d’Hebron and Networked Biomedical Research Center, Barcelona, Spain).

The 99.3% viral suppression rate after 7 years of TDF treatment was seen in hepatitis B e-antigen (HBeAg)-positive (99.4%) and HBeAg-negative patients (99.3%).

Serum alanine aminotransferase normalisation was achieved by 80% of patients who had abnormal levels at baseline, including 74.2% of HBeAg-positive and 83.5% of HBeAg-negative patients. Among those who did not achieve alanine aminotransferase normalisation, the median levels achieved were 51 U/L and 49 U/L, respectively.

HBeAg loss was seen in 54.5% of 154 HBeAg-positive patients after 7 years of TDF treatment and 39.6% experienced HBeAg seroconversion. The researchers also note that 11.8% of HBeAg-positive patients had hepatitis B s-antigen loss, which is consistent with rates reported for other antiviral agents.

TDF treatment was well-tolerated over the 7-year period, with grade 3 to 4 drug-related adverse events uncommon, renal adverse events infrequent and generally mild and corrected with dose modification, and no evidence of bone loss over 3 years of evaluation.

“[O]ur 7-year follow-up is the first [chronic hepatitis B] study to show that long-term use of an oral nucleos(t)ide agent—TDF monotherapy for chronic HBV infection—is able to suppress viral replication without development of resistance and is well tolerated”, the researchers conclude in Digestive Diseases and Sciences.

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