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BACKGROUND:
Emtricitabine is a nucleoside analogue approved for treatment of human
immunodeficiency virus 1 with clinical activity against hepatitis B virus (HBV).
METHODS:
To compare the safety and efficacy of emtricitabine with placebo in patients
with HBV, we conducted a randomized (2:1), double-blind study at 34 sites in
North America, Asia, and Europe that enrolled adults between November 2000
and July 2002 who had chronic HBV infection but had never been exposed to
nucleoside or nucleotide treatment. Each patient received either 200 mg of
emtricitabine (n=167) or placebo (n=81) once daily for 48 weeks and
underwent a pretreatment and end-of-treatment liver biopsy. Histologic
improvement was defined as a 2-point reduction in Knodell necroinflammatory
score with no worsening in fibrosis.
RESULTS:
At the end of treatment, 103 (62%) of 167 patients receiving active
treatment had improved liver histologic findings vs 20 (25%) of 81 receiving
placebo (P<.001), with significance demonstrated in subgroups positive
(P<.001) and negative (P=.002) for hepatitis Be (HBe) antigen. Serum HBV DNA
readings showed less than 400 copies/mL in 91 (54%) of 167 patients in the
emtricitabine group vs 2 (2%) of 81 in the placebo group (P<.001); alanine
aminotransferase levels were normal in 65% (109/167) vs 25% (20/81),
respectively (P<.001). At week 48, 20 (13%) of 159 patients in the
emtricitabine group with HBV DNA measured at the end of treatment had
detectable virus with resistance mutations (95% confidence interval,
8%-18%). The rate of seroconversion to anti-HBe (12%) and HBe antigen loss
were not different between arms. The safety profile of emtricitabine during
treatment was similar to that of placebo. Posttreatment exacerbation of HBV
infection developed in 23% of emtricitabine-treated patients.
CONCLUSION:
In patients with chronic HBV, both positive and negative for HBe antigen, 48
weeks of emtricitabine treatment resulted in significant histologic,
virologic, and biochemical improvement.
Reference:
Arch Intern Med. 2006 Jan 9;166(1):49-56. |