In China, HIV-1-infected patients typically receive antiretroviral therapy (ART) that includes lamivudine (3TC) as a reverse-transcriptase inhibitor (RTI) (ART-3TC). Previous studies from certain developed countries have shown that, in ART-3TC, 3TC-resistant HBV progressively emerges at an annual rate of 15–20% in patients coinfected with HIV-1 and HBV. This scenario in China warrants investigation because >10% of all HIV-infected patients in China are HBV carriers. We measured the occurrence of 3TC-resistant HBV during ART-3TC for HIV-HBV coinfection and also tested the effect of tenofovir disoproxil fumarate (TDF) used as an additional RTI (ART-3TC/TDF) in a cohort study in China. We obtained 200 plasma samples collected from 50 Chinese patients coinfected with HIV-1 and HBV (positive for hepatitis B surface antigen) and examined them for the prevalence of 3TC-resistant HBV by directly sequencing PCR products that covered the HBV reverse-transcriptase gene. We divided the patients into ART-3TC and ART-3TC/TDF groups and compared the efficacy of treatment and incidence of drug-resistance mutation between the groups. HIV RNA and HBV DNA loads drastically decreased in both ART-3TC and ART-3TC/TDF groups. In the ART-3TC group, HBV breakthrough or insufficient suppression of HBV DNA loads was observed in 20% (10/50) of the patients after 96-week treatment, and 8 of these patients harbored 3TC-resistant mutants. By contrast, neither HBV breakthrough nor treatment failure was recorded in the ART-3TC/TDF group. All of the 3TC-resistant HBV mutants emerged from the cases in which HBV DNA loads were high at baseline. Our results clearly demonstrated that ART-3TC is associated with the emergence of 3TC-resistant HBV in patients coinfected with HIV-1 and HBV and that ART-3TC/TDF reduces HBV DNA loads to an undetectable level. These findings support the use of TDF-based treatment regimens for patients coinfected with HIV-1 and HBV.
China-Japan Joint Laboratory of Molecular Immunology & Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China;Research Center for Asian Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan;Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. China;Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. China;Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. China;Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. China;China-Japan Joint Laboratory of Molecular Immunology & Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China;China-Japan Joint Laboratory of Molecular Immunology & Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China;China-Japan Joint Laboratory of Molecular Immunology & Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China;Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. China;China-Japan Joint Laboratory of Molecular Immunology & Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China;Research Center for Asian Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan;Research Center for Asian Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan;Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan;China-Japan Joint Laboratory of Molecular Immunology & Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China;CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China;CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China;Research Center for Asian Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan;Research Center for Asian Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan;Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan;Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, P.R. China;China-Japan Joint Laboratory of Molecular Immunology & Molecular Microbiology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P.R. China;Research Center for Asian Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Recommended Citation:
Lijun Gu,Yang Han,Yijia Li,et al. Emergence of Lamivudine-Resistant HBV during Antiretroviral Therapy Including Lamivudine for Patients Coinfected with HIV and HBV in China[J]. PLOS ONE,2015-01-01,10(8)