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.


  1. McMahon M et al. The anti-hepatitis B drug entecavir inhibits HIV-1 replication and selects HIV-1 variants resistant to antiretroviral drugs. Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, abstract 136LB, 2007
  2. McMahon M et al. The anti-hepatitis B drug entecavir inhibits HIV-1 replication and selects HIV-1 variants resistant to antiretroviral drugs. Fourteenth Conference on Retroviruses and Opportunistic Infections, Los Angeles, abstract 136LB, 2007
  3. McMahon M et al. The HBV drug entecavir - effects on HIV-1 replication and resistance. N Engl J Med 356 (25): 2614-2621, 2007
  4. Nagasaki F et al. The high incidence of the emergence of entecavir-resistant mutants among patients infected with lamivudine-resistant hepatitis B virus. Tohoku J Exp Med 213 (2): 181-186, 2007
  5. Pessoa W et al. Entecavir in HIV / HBV-co-infected patients: safety and efficacy in a phase II study (ETV-038). Twelfth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 123, 2005

Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.