[8, 9] Lamivudine,

(2′,3′-dideoxy-3′-thiacytidine, commonly known as 3TC) was the initial oral nucleoside analog reverse transcriptase inhibitor, used in CHB to inhibit HBV DNA synthesis. Lamivudine is phosphorylated to active metabolites, which compete for incorporation into viral DNA; it is rapidly absorbed with an excellent bioavailability of > 80%.[9, 10] This drug has been reported to effectively prevent disease progression in patients with high HBV DNA levels and cirrhosis.[11] The major drawback of this agent lies with its high rates of drug resistance; this typically develops at a rate of up to 25% of patients per year and reaching 80% by 4 years.[12, 13] Lamivudine resistance Opaganib is related to the emergence of mutations in the YMDD motif PARP inhibitor (rtM204V/I) (tyrosine, methionine, aspartate, aspartate) of HBV DNA polymerase domain C as well as in (upstream) compensatory mutations in the polymerase domains A and B, that collectively limit the drug’s clinical efficacy. The rate of genotypic resistance is reported to increase from 14% to 32% at 1 year,

to 70% at 5 years.[9, 14] Antiviral resistance can manifest in manifold ways, most commonly as virological breakthrough (> 1 log10 increase in HBV DNA level from nadir in a medication compliant patient). This scenario is usually followed by biochemical breakthrough (elevated ALT), and in some instances acute hepatitis flare and/or liver failure[9, 14] However, in select groups of HBV-infected patients, successful long-term viral suppression has been achieved using lamivudine

with low treatment failure rates. With strict dosing adherence and monitoring for virological breakthrough, sustained virological suppression can still be reliably achieved with this agent.[15] Because of cross-resistance between several oral antiviral agents and the emergence medchemexpress of lamivudine resistance, switching to alternative agents such as telbivudine and entecavir, would be imprudent.[16] Of greater concern is the emergence of drug-resistant strains, which can significantly put global hepatitis B immunization initiatives at risk. Mutations associated with drug treatment can cause changes to the hepatitis B surface antigen (HBsAg) protein, the component of the virus that the hepatitis B vaccine mimics.[16] Despite its limitations, lamivudine remains the mainstay treatment of CHB in many developing countries because of its safety, efficacy and affordability. Adefovir dipivoxil is another antiviral agent available in the drug armamentarium; however, its utility has been limited by the development of significant drug resistance, reported at 30% by the end of 4 years.[17] It has also lost appeal by virtue of poorer potency and slower rates of HBV DNA suppression.