Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naive and -experienced patients coinfected with HIV-1 and hepatitis B virus

J Infect Dis. 2004 Apr 1;189(7):1185-92. doi: 10.1086/380398. Epub 2004 Mar 12.

Abstract

Background: Coinfection with human immunodeficiency virus type 1 (HIV-1) increases the risk of hepatitis B virus (HBV)-associated progressive liver disease. Lamivudine has potent activity against both HIV-1 and HBV; however, lamivudine-resistance mutations in HBV frequently develop.

Methods: Substudies of the safety and efficacy of tenofovir disoproxil fumarate (tenofovir DF) for patients coinfected with HIV and HBV were undertaken within 2 phase 3 randomized controlled trials involving antiretroviral therapy-experienced (study 907) and -naive (study 903) HIV-infected populations. Inclusion criteria were detection of hepatitis B surface antigen, an HBV DNA level >106 copies/mL at baseline, and HBV DNA specimens available at week 24 (study 907) and week 48 (study 903).

Results: In study 907, the mean decrease in HBV DNA was 4.9 log(10), after 24 weeks, for 10 patients randomized to receive tenofovir DF, compared with a mean increase of 1.2 log(10) for 2 patients randomized to receive placebo (P=.041). The mean decrease in HBV DNA during tenofovir DF treatment was similar for patients with wild-type (5.3 log(10)) and lamivudine-resistant (4.6 log(10)) HBV strains. In study 903, the mean decrease in HBV DNA was 3.0 log(10), after 48 weeks, for 6 patients randomized to receive lamivudine, compared with 4.7 log(10) for 5 patients randomized to receive lamivudine and tenofovir DF (P=.055). Four patients developed tyrosine-methionine-aspartate-aspartate mutations, all in the lamivudine-only treatment arm.

Conclusion: Tenofovir DF has potent anti-HBV efficacy in antiretroviral therapy-experienced and -naive individuals coinfected with HIV and HBV.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / therapeutic use*
  • Adult
  • Alanine Transaminase / blood
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1* / genetics
  • HIV-1* / growth & development
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus* / genetics
  • Hepatitis B virus* / growth & development
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Male
  • Mutation
  • Organophosphonates*
  • Organophosphorus Compounds / therapeutic use*
  • Tenofovir

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Organophosphonates
  • Organophosphorus Compounds
  • Tenofovir
  • Alanine Transaminase
  • Adenine