Antiviral therapy: nucleotide and nucleoside analogs.
For the management of HBV infection, an increasing number of nucleotide and nucleoside analogs are active against wild-type HBV and some against HBV with YMDD and other compensatory mutations. Table 2 depicts the IC50 and susceptibilities of HBV to various antiviral agents. The dichotomy between in vitro and in vivo susceptibilities to YMDD mutants is due to a change in IC50 between wild-type and mutant virus. Thus a drug may have less activity in vitro but at doses used in vivo show activity against YMDD and other compensatory mutations. Some HBV drugs share activity against HIV, which may be useful in the co-infected patient. Other nucleoside analogs are in various stages of development, including MCC-478 and DAPD. In the future, clinicians will have a plethora of reagents to chose from, and combination therapies may be invoked.
Department of Clinical Pharmacy, University of California, San Francisco, 521 Parnassus Avenue, Room C-152, Box 0622, San Francisco, CA 94143-0622, USA.
David J
DJ
Quan
Marion G
MG
Peters
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004148:Dioxolanes / Q000494:pharmacology / Q000627:therapeutic use; D006509:Hepatitis B / Q000188:drug therapy*; D006515:Hepatitis B virus; D006801:Humans; D020128:Inhibitory Concentration 50; D017354:Point Mutation; D011684:Purine Nucleosides / Q000494:pharmacology / Q000627:therapeutic use; D011687:Purines / Q000494:pharmacology / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects
C461207:2-amino-6-(4-methoxyphenylthio)-9-(2-(phosphonomethoxy)ethyl)purine bis(2,2,2-trifluoroethyl) ester; D000998:Antiviral Agents; D004148:Dioxolanes; D011684:Purine Nucleosides; D011687:Purines; D018894:Reverse Transcriptase Inhibitors; C098393:amdoxovir