Telbivudine, the prototype member of beta-L-2 -deoxynucleosides, has proven to be safe in in vitro animal and human studies. Telbivudine given for 4 weeks resulted in an 8-log reduction of woodchuck hepatitis virus DNA, and a 3.8-log reduction of hepatitis B virus DNA in human. After 52 weeks of telbivudine treatment there was an approximate 6-log reduction of hepatitis B virus DNA levels, hepatitis B virus DNA became undetectable by PCR assay in 61 of patients. Its antiviral efficacy is significantly better than lamivudine. The probability of tyrosine-methionine-aspartate-aspartate mutations at 52 weeks of telbivudine therapy is low, although still occurring in 4.5 of patients. After 96 weeks of therapy, the proportion of patients with undetectable hepatitis B virus DNA by PCR assay increased to 71, but genotypic resistance also increased to 18.2, with only 4.5 showing alanine aminotransferase flares. Telbivudine is probably one of the most potent antiviral agents for hepatitis B virus that will become available in the near future.
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