The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients

AIDS. 2008 May 11;22(8):947-55. doi: 10.1097/QAD.0b013e3282ffde91.

Abstract

Background: Entecavir, an antiviral with potent anti-hepatitis B virus activity, was recently shown to have anti-HIV activity in three patients and the ability to select for the lamivudine-resistant HIV polymerase mutation M184V in a patient with prior antiretroviral therapy.

Objectives: To further characterize entecavir's anti-HIV activity and identify risk factors for selection of the M184V.

Design: Retrospective cohort study.

Methods: We evaluated the virological characteristics of HIV and hepatitis B virus in 17 HIV-hepatitis B virus coinfected patients (10 antiretroviral therapy-naive and seven antiretroviral therapy-experienced) prior to and during entecavir monotherapy. Descriptive statistics were used to assess changes in HIV RNA and hepatitis B virus DNA. Variables associated with development of the M184V were determined by univariate analysis.

Results: Of the 17 patients, 13 (76%) demonstrated a reduction in HIV RNA by at least 0.5 log10 copies/ml. Of the remaining four patients, two had the M184V detected prior to entecavir therapy and the other two had wild-type HIV. The median reduction in HIV RNA for the cohort was 1.2 log10 copies/ml, which was similar in antiretroviral therapy-naive and antiretroviral therapy-experienced patients. The M184V mutation emerged in six patients receiving entecavir, including three antiretroviral therapy-naive patients. No other HIV mutations were consistently detected. Risk factors for the emergence of the M184V mutation were a decline in hepatitis B virus DNA (P = 0.04) and duration of entecavir use (P = 0.05).

Conclusion: Entecavir monotherapy in HIV-hepatitis B virus coinfected patients, including antiretroviral therapy-naive patients, has significant anti-HIV activity and can result in the development of the M184V variant. Entecavir should not be used in such co-infected patients without concomitant antiretroviral therapy.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiviral Agents / therapeutic use
  • CD4 Lymphocyte Count
  • DNA, Viral / blood
  • Drug Evaluation
  • Drug Resistance, Viral / genetics
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / therapeutic use
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV Reverse Transcriptase / antagonists & inhibitors
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / drug effects
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / drug therapy*
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Mutation
  • RNA, Viral / blood
  • Retrospective Studies
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Risk Factors

Substances

  • Anti-HIV Agents
  • Antiviral Agents
  • DNA, Viral
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Lamivudine
  • entecavir
  • Guanine
  • HIV Reverse Transcriptase