title: The anti-HIV activity of entecavir: a multicentre evaluation of lamivudine-experienced and lamivudine-naive patients.
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.
  
  
  OBJECTIVE
  To further characterize entecavir's anti-HIV activity and identify risk factors for selection of the M184V.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Alfred Hospital, Melbourne, Victoria, Australia. joe.sasadeusz@mh.org.au
authors.forename: Joe
authors.initials: J
authors.lastname: Sasadeusz
authors.forename: Jennifer
authors.initials: J
authors.lastname: Audsley
authors.forename: Anne
authors.initials: A
authors.lastname: Mijch
authors.forename: Rachel
authors.initials: R
authors.lastname: Baden
authors.forename: Jose
authors.initials: J
authors.lastname: Caro
authors.forename: Hermeyone
authors.initials: H
authors.lastname: Hunter
authors.forename: Gail
authors.initials: G
authors.lastname: Matthews
authors.forename: Moira A
authors.initials: MA
authors.lastname: McMahon
authors.forename: Susan A
authors.initials: SA
authors.lastname: Olender
authors.forename: Robert F
authors.initials: RF
authors.lastname: Siliciano
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Lewin
authors.forename: Chloe L
authors.initials: CL
authors.lastname: Thio
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004279:DNA, Viral / Q000097:blood; D004341:Drug Evaluation; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000187:drug effects / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D004279:DNA, Viral; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D054303:HIV Reverse Transcriptase