Tenofovir monotherapy effective for entecavir-resistant HBV

Last Updated: 2015-05-13

By Lorraine L Janeczko

NEW YORK (Reuters Health) - For entecavir-resistant hepatitis B virus (HBV) infection, tenofovir alone appears to be as effective as a tenofovir/entecavir combination, new research from Korea suggests.

"Our data suggest that TDF (tenofovir disoproxil fumarate) monotherapy can be a safe and efficacious option for the treatment of hepatitis B patients regardless of previous exposure to other drugs or pre-existing resistance profile," wrote lead author Dr. Young-Suk Lim of the University of Ulsan College of Medicine in Seoul, in an email to Reuters Health.

The 48-week randomized trial involved 90 HBV patients with entecavir (ETV) resistance-associated mutations and serum HBV DNA concentrations >60 IU/mL.

As reported online April 30 in Gut, everyone received 300 mg/day of TDF (Viread, Gilead Sciences, Inc.) and 45 also received 1 mg/day of ETV (Baraclude, Bristol-Myers Squibb).

At week 48, the proportion of patients who reached the primary efficacy endpoint of HBV DNA <15 IU/mL was similar with TDF vs TDF+ETV (71% vs 73%). The mean change in HBV DNA levels from baseline was also similar (3.66 vs 3.74 log10 IU/mL).

One patient on monotherapy had virological breakthrough, which the authors attributed to poor drug adherence.

At week 48, six and three patients in the TDF and TDF+ETV groups, respectively, maintained their baseline resistance mutations (p>0.99) and none developed additional resistance mutations.

Safety profiles were similar in both groups, according to the report.

"Even if HBV replication is completely suppressed, very few patients achieve HBsAg (hepatitis B surface antigen) seroclearance, which is the closest to a hepatitis B cure," Dr. Lim wrote in an email. "So to prevent liver disease progression, most patients require long-term nucleoside/nucleotide (NUC)."

Long-term combination therapy may also carry a higher risk of adverse events and drug-drug interaction as well as higher inconvenience and cost than monotherapy, he added.

"Many patients worldwide have developed drug resistance from the widespread use of less potent NUCs, such as lamivudine (LAM) or adefovir dipivoxil (ADV), which have a low genetic barrier to resistance," he wrote.

"Most current practice guidelines recommend combination therapy for patients with drug-resistant HBV. However, the evidence level has been low," Dr. Lim wrote. "We think that our study results provide a high level of evidence to change the guidelines. In fact, World Health Organization and Asia-Pacific guidelines are being revised to recommend TDF monotherapy for patients with drug-resistant HBV."

Dr. Anna Lok of the University of Michigan Health System in Ann Arbor, who was not involved in the study, wrote in an email, "It was important to do this study because, if one drug is as effective as two drugs, we can have major cost savings. Other patients with entecavir-resistant HBV can be treated with tenofovir monotherapy, greatly reducing cost."

The study will continue, Dr. Lim wrote. "The proportion of patients with virologic response of TDF monotherapy and TDF+ETV combination therapy was not satisfactory, about 65% after up to 96 weeks. Although none of the patients acquired emergence of additional resistance HBV mutants, the results suggest that long-term close observation is needed. Thus, the research will be extended up to 240 weeks."

Gilead Sciences, Inc., which supplied the study drug, and the Korean Health Technology Research and Development Project of the Ministry of Health and Welfare supported the study.

Dr. Lim and one coauthor have financial relationships with both Bristol-Myers Squibb and Gilead Sciences, as does Dr. Lok.

SOURCE: http://bit.ly/1Je1aiJ

Gut 2015.