Duration of Therapy for Treating HBV

In a poster presentation at CROI 2009 in Montreal, Canada, the French INSERM UMR-S707 study examined the level of liver fibrosis, over time, among 130 HIV-positive people taking tenofovir for hepatitis B disease (HBV). Fibrosis is the development of an excessive amount of fibrous connective tissue. The most severe fibrosis is cirrhosis, or scarring of the liver.

The risk of living long-term with cirrhosis, especially its severe forms, is liver cancer. The French team looked at volunteers upon study entry (baseline) and every 12 months thereafter to determine the stage of fibrosis. Stage 0 is no fibrosis and stage 1 is very minimal. Stages 2 through 4 are more serious, with stage 4 fibrosis being cirrhosis.

The group showed significant decreasing levels of fibrosis after nearly 30 months of tenofovir therapy, which supports a rethinking of how long anti-HBV therapy should last. Among people with stages 0 through 2, their levels remained stable over time. Among those with more severe fibrosis (stages 3 and 4), there was a steep decline in HBV levels through one year of therapy followed by a slow and stable continued decline through the second and third years on therapy. At least among people with more serious fibrosis, if these data are confirmed by other studies, extended use of therapy may be warranted.

A separate study looked at the development of HBV resistance to tenofovir over a two-year period. Among 88 people who took tenofovir for two years, 75 had undetectable HBV levels and 5 had persistent, detectable low levels of HBV. Among those 5, no specific mutation conferring resistance to tenofovir was identified. More research is needed to evaluate the long-term use and potential resistance issues with this therapy.