The HBV drug entecavir - effects on HIV-1 replication and resistance

N Engl J Med. 2007 Jun 21;356(25):2614-21. doi: 10.1056/NEJMoa067710.

Abstract

Entecavir, a drug approved by the Food and Drug Administration for the treatment of chronic hepatitis B virus (HBV) infection, is not believed to inhibit replication of human immunodeficiency virus type 1 (HIV-1) at clinically relevant doses. We observed that entecavir led to a consistent 1-log(10) decrease in HIV-1 RNA in three persons with HIV-1 and HBV coinfection, and we obtained supportive in vitro evidence that entecavir is a potent partial inhibitor of HIV-1 replication. Detailed analysis showed that in one of these patients, entecavir monotherapy led to an accumulation of HIV-1 variants with the lamivudine-resistant mutation, M184V. In vitro experiments showed that M184V confers resistance to entecavir. Until more is known about HIV-1-resistance patterns and their selection by entecavir, caution is needed with the use of entecavir in persons with HIV-1 and HBV coinfection who are not receiving fully suppressive antiretroviral regimens.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Guanine / therapeutic use
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Hepatitis B / complications
  • Hepatitis B / drug therapy*
  • Hepatitis B virus
  • Humans
  • Lamivudine / therapeutic use
  • Male
  • Middle Aged
  • Mutation
  • Phylogeny
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Reverse Transcription / drug effects
  • Virus Replication / drug effects*
  • Zidovudine / therapeutic use

Substances

  • Antiviral Agents
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • Zidovudine
  • entecavir
  • Guanine
  • HIV Reverse Transcriptase