Entecavir (Baraclude)

Entecavir is a nucleoside analogue drug (a guanosine analogue) used as an antiviral treatment for hepatitis B. As entecavir was originally thought to have selective activity against hepatitis B virus (HBV) polymerase only, it has been the recommended therapy for HBV treatment in people with HIV-HBV co-infection. However, a research team recently reported that entecavir is also an inhibitor of HIV reverse transcriptase (RT), after observing HIV viral load drops in co-infected patients who began entecavir treatment.^{1 2}

In some such patients, entecavir use has selected for the M184V mutation in HIV, conferring cross-resistance to 3TC (lamivudine) and FTC (emtricitabine). The manufacturer Bristol-Myers Squibb has issued a press release and added a black box warning to the package insert regarding this danger.

Entecavir should not be used alone in HIV/HBV co-infected patients whose HIV is not suppressed. It is, at best, a partial inhibitor of HIV, creating selective pressure and a favourable environment for HIV resistance to develop, even at high entecavir concentrations.³

Another option is to treat HIV/HBV co-infected patients with multiple anti-HBV drugs, thus slowing the emergence of resistance to a single agent. Finally, reconsideration could be given to starting such individuals on antiretroviral therapy along with anti-HBV therapy, with regular monitoring for hepatotoxicity since patients who require hepatitis B treatment may have advanced liver disease.

Another study points out the possibility that the usage of entecavir for lamivudine-resistant HBV could promptly induce entecavir-resistant mutations in addition to lamivudine-resistance.⁴

Entecavir works by inhibiting the hepatitis B virus’s enzyme DNA polymerase, preventing new viruses from being made. It was approved for marketing in the United States in March 2005 and in the European Union in June 2006.

The approval for hepatitis B mono-infected patients was based on data from one year of treatment in nucleoside-treatment-naive and 3TC-resistant adult patients with hepatitis B e antigen-positive, or -negative, chronic hepatitis B infection with compensated liver disease. Entecavir was more effective than 3TC in patients with no treatment experience, as well as those with 3TC resistance

The approval for HIV co-infected patients was based on more limited data from a randomised, double-blind, placebo-controlled study of entecavir versus placebo in 68 individuals co-infected with HIV and hepatitis B. All of the patients had experienced recurrence of hepatitis B viral load while receiving an antiretroviral therapy regimen containing 3TC. After 24 weeks, the mean hepatitis B viral load fell by 3.66 log₁₀ with entecavir but rose by 0.11 log₁₀ in the placebo group.⁵

Entecavir’s side-effects include headache, tiredness, dizziness, nausea and infections of the respiratory tract.

The recommended dose of entecavir for chronic hepatitis B virus infection in nucleoside analogue treatment-naive adults and adolescents 16 years of age and older is 0.5mg once a day. For patients with a history of detectable hepatitis B viral loads while receiving 3TC or known 3TC resistance mutations, the recommended dose is 1mg once a day. The higher dose must be taken at least two hours before or two hours after a meal.