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To determine if highly active antiretroviral therapy (HAART) with combination anti-hepatitis B virus (HBV) therapy compared to HAART with HBV monotherapy leads to greater HBV DNA suppression in an HIV/HBV coinfected cohort.A cross-sectional analysis of 122 HIV/HBV coinfected patients from Australia and the United States.Univariate analysis and ordinal logistic regression were used to determine factors associated with an HBV DNA less than 100 IU/ml.The majority of patients were on HAART (85%), had an HIV RNA less than 50 copies/ml, a median CD4 cell count of 438 cells/μl, and had prior or current lamivudine therapy (98%). The majority (89%) of those on HAART were on HBV-active drugs including 54% on tenofovir (TDF) with either lamivudine (LAM) or emtrictabine (FTC), 34% receiving LAM or FTC monotherapy, and 12% on TDF monotherapy. Only 4% of patients in the combination (TDF + LAM/FTC) group had HBV DNA greater than 20 000 IU/ml compared to 54% in the group on no HBV-active therapy, 31% in the LAM or FTC monotherapy group, and 30% in the TDF monotherapy group (P < 0.0001). In an ordinal logistic regression model, monotherapy with either TDF or LAM remained independently associated with higher HBV DNA.These data suggest that there may be an advantage to using TDF in combination with LAM or FTC in HIV/HBV coinfection, particularly in the setting of previous LAM experience. Continued prospective follow-up in this study will confirm whether the advantage is sustained longer-term.