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AASLD 2013: Tenofovir for Hepatitis B Remains Safe and Effective Over 7 Years

Chronic hepatitis B patients treated with tenofovir (Viread) for 7 years continued to main viral suppression and liver enzyme normalization, while serological response rates continued to increase, according to a poster presented at the 64th AASLD Liver Meeting last month in Washington, DC. Long-term kidney and bone-related side effects remained uncommon.

Nucleoside/nucleotide antivirals such as tenofovir disoproxil fumarate or entecavir (Baraclude) effectively suppress hepatitis B virus (HBV) replication, but they usually do not eradicate the virus and may need to be taken long term.

Patrick Marcellin from the University of Paris and colleagues presented the latest findings from Study 102 and Study 103, a pair of Phase 3 trials that evaluated tenofovir in hepatitis B "e" antigen (HBeAg) negative and positive patients, respectively.

In both trials, participants were randomly assigned to receive 300 mg once-daily tenofovir or 10 mg adefovir (Hepsera) for 1 year, after which they could elect to continue on open-label tenofovir for up to 8 years. People with continued detectable virus despite tenofovir had the option to add emtricitabine (Emtriva).

Together, the studies enrolled more than 600 treatment-naive participants; 437 (68%) were still being followed at year 7. About three-quarters were men, about 60% were white, 30% were Asian, and the mean age was approximately 40 years. Just under 25% had liver cirrhosis.

Results

• Rates of viral suppression (HBV DNA <400 copies/mL) remained high in an intent-to-treat analysis:

o   HBeAg negative: 77% at year 7 vs 81% at year 6;

o   HBeAg positive: 60% at year 7 vs 63% at year 6.

• Among people who remained on treatment, 7-year viral suppression rates were 99% in both studies.
• Biochemical response rates, or alanine aminotransferase (ALT) normalization, were higher for HBeAg negative patients:

o   HBeAg negative: 65% at year 7 vs 70% at year 6;

o   HBeAg positive: 47% at year 7 vs 51% at year 6.

• Among people who remained on treatment, 7-year ALT normalization rates were 84% in Study 102 and 74% in Study 103.
• Serological response rates in Study 103 continued to rise, with 55% experiencing HBeAg loss and 40% having HBeAg seroconversion at 7 years.
• Hepatitis B surface antigen (HBsAg) changes remained uncommon: 12% HBsAg loss and 10% anti-HBs seroconversion in Study 103, and 1 individual with confirmed HBsAg loss/seroconversion at week 240 in Study 102.
• 4 people with detectable viral load qualified for genotypic analysis; no conserved site mutations and 1 polymorphic site change was detected.
• Tenofovir remained safe and well-tolerated.
• There were no new drug-related adverse events during year 7.
• 2 people experienced kidney-related events -- increased serum creatinine and elevated phosphate -- but no additional patients had creatinine clearance <50 mL/min.
• No significant changes in mean bone mineral density at the hip or lumbar spine, and no consistent trends in T-scores, were observed between year 4 (when DEXA scans were started) and year 7.

"Virologic, biochemical, and serologic responses [to tenofovir] were well maintained through 7 years," the researchers concluded. "No resistance to [tenofovir] was detected through 7 years."

12/4/13

Reference

P Marcellin, EJ Gane, N Tsai, et al. Seven Years of Treatment with Tenofovir DF for Chronic Hepatitis B Virus Infection is Safe and Well Tolerated and Associated with Sustained Virological, Biochemical, and Serological Responses with no Detectable Resistance. 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2013). Washington, DC, November 1-5, 2013. Abstract 926.