Protective effect of hepatitis B virus-active antiretroviral therapy against primary hepatitis B virus infection

AIDS. 2014 Apr 24;28(7):999-1005. doi: 10.1097/QAD.0000000000000180.


Objective: Current guidelines advise to vaccinate every hepatitis B virus (HBV)-susceptible HIV patient against HBV until sufficient antibody titers have been reached. However, in this era of combination antiretroviral therapy (cART), acute HBV infection rarely occurs in patients who lack this immune protection. We analyzed whether HBV-active cART (lamivudine, emtricitabine, tenofovir) might work as a preexposure prophylaxis (PrEP) to explain this effect.

Methods: From our HIV cohort at the Onze Lieve Vrouwe Gasthuis hospital (N=2942), patients were selected retrospectively for negative HBV serology (HBsAg, anti-HBs and anti-HBc-negative) at cohort entry. Men who have sex with men (MSM) with a second HBV serology available were included for analysis. The incidence of anti-HBc conversion was determined and correlated with the use of HBV-active drugs. Kaplan-Meier curves and log-rank tests were used to compare HBV-free survival for MSM.

Results: In total, 33 HBV infections occurred in 381 eligible MSM over a median follow-up of 2470 days (interquartile range 1146-3871.5). The incident rate per 100 patient-years of follow-up was 1.10 overall, but differed strongly dependent on the use of HBV-active drugs: 2.85/100 patient-years of follow-up in the absence of HBV-active drugs, 1.36 when only lamivudine was used, and 0.14 in the presence of tenofovir. Furthermore, HBV-free survival rate was significantly higher when HBV-active cART was used, in particular when this HBV-active cART contained tenofovir (log-rank P<0.001).

Conclusion: Our findings demonstrate that HBV-active cART protects against the occurrence of de-novo HBV infection, most strongly when tenofovir is used.

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • Cohort Studies
  • HIV Infections / drug therapy*
  • Hepatitis B / epidemiology
  • Hepatitis B / prevention & control*
  • Hepatitis B Antibodies / blood
  • Hepatitis B Core Antigens / immunology
  • Humans
  • Incidence
  • Male
  • Pre-Exposure Prophylaxis / methods*
  • Retrospective Studies
  • Survival Analysis
  • Time Factors


  • Anti-Retroviral Agents
  • Hepatitis B Antibodies
  • Hepatitis B Core Antigens