Jing Li,1 Donghua Zhang,1 Xinxin Zhang1,2 1Department of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Sino-French Research Centre for Life Sciences and Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Xinxin ZhangDepartment of Infectious Diseases, Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, People’s Republic of ChinaTel +86 21-64370045 ext 681088Email zhangx@shsmu.edu.cnAbstract: Tenofovir disoproxil fumarate (TDF) is recommended as first-line agents in chronic hepatitis B (CHB) patients for its high antiviral effects and high barrier to resistance. It is controversial whether the rtA194T mutation truly confers resistance against TDF. We present here a 62-year-old CHB patient who occurred rtL180M, rtM204V and rtA194T mutants after lamivudine (LAM) monotherapy for 9 years. TDF was introduced in replacement of LAM and led to Hepatitis B Virus (HBV) DNA undetectable in 1 month, maintained in the follow up of 52 weeks. These observations suggest that rtA194T mutation emerges under LAM monotherapy and remains sensitive to TDF.Keywords: hepatitis B, tenofovir disoproxil fumarate, resistance, rtA194T mutant, case report