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BackgroundHepatitis B infection is a worldwide health concern infecting more than 400 million people worldwide. Besides the active immunization program of WHO, the role of antivirals for treating the chronic infection is inevitable. The tribal belt of Pakistan is the most affected part in war against terror. In addition to lack of basic facilities and resources, this part of country has also been neglected for various health related studies. In this study we report the efficacy of the commonly used antivirals; Entecavir (ETV) and Tenofovir Disoproxil Fumarate (TDF).MethodsA total of 2875 HBV infected patients (Male = 1500 and Female = 1375) of different age groups who were receiving either ETV as monotherapy or ETV plus TDF were followed up for 6 and 12 months. Viral DNA was extracted from serum followed by amplification and detection with MyGo Real-Time thermocycler and Gene Proof PCR kit. Response towards antivirals was analyzed statistically with Pearson’s Chi Square test. ResultsComparable response (p=0.171) was observed among the HBV patients towards both six (27%) and twelve month antiviral therapy (36%). Duration of antiviral therapy improved the rate of response in male and patients of old age (p=0.001 & ConclusionOur findings demonstrate that the ETV monotherapy and ETV plus TDF combination therapy are not effective for the HBV infection because both do not achieve SVR rate even in 50% of patients following six and twelve-month follow-up. Therefore, there is a need of much more effective antiviral drugs to treat HBV infection in the study area.