Background:  Entecavir (ETV) is a potent and selective inhibitor of hepatitis B virus (HBV) polymerase with a low interaction potential with HIV medications, and does not select for ART-resistant HIV. We hypothesized that ETV would be superior to placebo in reducing HBV DNA in HIV/HBV-co-infected patients who experienced recurrent HBV viremia while receiving lamivudine (3TC)-containing HAART. ETV may be a future anti-HBV treatment option of particular interest for HIV⁺ co-infected patients.

Methods:  ETV-038 is an ongoing, double blind, comparative trial involving 68 HIV/HBV-co-infected patients who experienced HBV viremia during treatment with 3TC, the majority of whom (88%) carried HBV with at least 1 3TC-resistance mutation. Patients were randomized to receive either ETV 1.0 mg (n = 51) or placebo (n = 17) once daily for 24 weeks, followed by open-label ETV for another 24 weeks. All patients continued taking 3TC throughout the study. The primary objective was to compare the mean reduction in HBV DNA levels from baseline in each treatment group at 24 weeks.

Results:  Mean baseline viral load was 9.13 log₁₀ copies/mL. At 24 weeks, the mean reduction in HBV DNA from baseline was superior in the ETV group compared with the placebo group (–3.66 vs +0.11 log₁₀ copies/mL, p < 0.0001). The proportion of patients with < 400 copies/mL or a ≥ 2 log₁₀ reduction from baseline was also superior with ETV (84% vs 0% for placebo, p < 0.0001). Significantly more ETV-treated patients achieved ALT normalization after 24 weeks than those given placebo (49% vs 17%, p = 0.05). After a mean follow-up of over 40 weeks, the overall frequency of adverse events was comparable between ETV and placebo. Two patients treated with ETV (4%) discontinued treatment because of adverse events. One patient discontinued due to elevated ALT and bilirubin, the other because of elevated ALT/AST. Both events were present at baseline and were considered not related to the study medication. No significant changes in HIV viremia nor in CD4 count were observed in either treatment group.

Conclusions:  In HIV/HBV-co-infected patients with 3TC-resistant HBV, adding ETV therapy results in rapid and clinically significant reductions in HBV DNA and normalization of ALT within 24 weeks, with comparable tolerability to placebo. No interference with HIV infection or HAART was observed. ETV is the first selective HBV antiviral to demonstrate safety and efficacy in this population.

Keywords: Entecavir; Lamivudine; HBV co-infection