The immune suppression caused by HIV infection accelerates the course of liver disease caused by chronic hepatitis B virus (HBV) infection. We assessed the outcome of HIV/HBV-coinfected patients exposed to highly active antiretroviral therapy (HAART) including anti-HBV active drugs. Baseline and follow-up plasma HBVDNA and HIV-RNA levels, HBV serological markers, and CD4 counts were longitudinally evaluated in all HBsAg(+) individuals with HIV infection on regular follow-up at an urban HIV reference clinic. Out of 79 HBsAg(+) chronic carriers identified, 39 (50%) were HBeAg(+). Lamivudine (3TC) alone had been received by 37% of patients, while 3TC plus tenofovir (concomitantly or consecutively) had been taken by 58% of them. The median follow-up was of 52 months. Loss of HBeAg or HBsAg occurred in 28% (10/36) and 13% (10/75) of patients, respectively. In multivariate analysis, only undetectable plasma HIV-RNA levels [OR 4.58 (95% CI 1.25-16.78); p = 0.02] and greater CD4 gains on HAART [OR 1.003 (95% CI 1.000-1.006); p = 0.03] were associated with undetectable serum HBV-DNA at the end of follow-up. Anti-HBV active HAART makes it possible to achieve HBsAg clearance, anti-HBe seroconversion, and suppression of HBV replication in a substantial proportion of HBV/HIV-coinfected patients, particularly in those with complete HIV suppression and greater immune recovery. Thus, HBV/HIV-coinfected patients might benefit from an earlier introduction of HAART.