AASLD 2014: Tenofovir Continues to Work Well Against Hepatitis B Virus for 8 Years

alt

Most chronic hepatitis B patients treated with tenofovir (Viread) for 8 years continued to maintain viral suppression, researchers reported at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting last week in Boston.Serological response rates continued to increase over time and kidney and bone-related side effects remained uncommon.

Nucleoside/nucleotide analog antivirals such as tenofovir, entecavir (Baraclude), adefovir (Hepsera), and lamivudine (Epivir) are the mainstay of chronic hepatitis B treatment. Although they can effectively suppress hepatitis B virus (HBV) replication while on therapy, they typically do not eradicate the virus and therefore may need to be taken long term. Viral suppression has been shown to improve liver fibrosis and reduce the risk of complications such as liver cancer.

Patrick Marcellin from Hôpital Beaujonin Paris and colleagues presented the latest findings from Gilead Sciences' Study 102 and Study 103, a pair of Phase 3 trials evaluating tenofovir in hepatitis B "e" antigen (HBeAg) negative and HBeAg positive patients, respectively.

Together, the studies enrolled more than 600 participants, most previously untreated. Nearly three-quarters were men, about 60% were white, about 30% were Asian, the mean age was approximately 40 years, and 24% had liver cirrhosis. A majority of HBeAg negative participants (64%) had HBV genotype D, with 11% having genotypes A, B, and C; genotypes were more evenly distributed in the HBeAg positive study.

Participants in both trials were randomly assigned to receive 300 mg tenofovir or 10 mg adefovir for 48 weeks, after which they could elect to continue on open-label tenofovir. People with continued detectable HBV DNA while on tenofovir had the option of adding emtricitabine (Emtriva) at week 72 or later. Safety and efficacy were assessed every 3 months, resistance testing was performed annually, and DEXA bone mineral density scans were performed starting at year 4 of follow-up.

About 90% of participants completed the initial blinded 48-week phase and entered the open-label phase. A total of 266 HBeAg negative patients (71% of those initially randomized and treated) and 146 HBeAg positive patients (55%) completed follow-up through week 384, or approximately 8 years -- the originally planned study duration.

Results

Over an 8-year period of treatment with tenofovir, "virologic and serologic responses were durable" and viral suppression was "consistently maintained," the researchers concluded.

"Renal events were uncommon," they added, and there was "no clinically relevant bone loss over 4-year follow-up."

Another study presented at the meeting found that adding pegylated interferon to tenofovir increased the likelihood of HBsAg loss.

11/19/14

Reference

P Marcellin, EJ Gane, R Flisiak, et al. Long Term Treatment with Tenofovir Disoproxil Fumarate for Chronic Hepatitis B Infection is Safe and Well Tolerated and Associated with Durable Virologic Response with no Detectable Resistance: 8 Year Results from Two Phase 3 Trials. American Association for the Study of Liver Diseases (AASLD) Liver Meeting. Boston, November 7-12, 2014. Abstract 229.