title: Failure of combination therapy with lamivudine and famciclovir following lamivudine monotherapy for hepatitis B virus infection in patients coinfected with human immunodeficiency virus-1.
abstract: Individuals coinfected with human immunodeficiency virus 1 (HIV-1) and hepatitis B virus (HBV) often receive treatment with an antiretroviral regimen including lamivudine. Lamivudine monotherapy for HBV may lead to drug-resistant mutations in a significant number of patients. The virological and biochemical responses of 8 patients coinfected with HBV/HIV-1 treated with both lamivudine and famciclovir were studied. Patients exhibiting HBV viral rebound at 1 year were analyzed for the emergence of HBV polymerase mutations. Only 1 patient had no prior exposure to lamivudine. Addition of famciclovir to the treatment regimen resulted in a median fall in HBV DNA level of 0.33 log(10) at 3 months and an overall rise in HBV DNA level of 3 log(10) at 12 months. The only patient in whom durable viral suppression and HBV e antigen seroconversion were noted began receiving lamivudine and famciclovir simultaneously. HBV polymerase gene sequencing identified resistance-associated mutations in 6 of 7 patients with viral rebound. Sequential nucleoside analogue therapy is unlikely to be successful in achieving long-term suppression of HBV replication, and combination therapy should be considered at treatment initiation.
authors.affiliation: Department of HIV Medicine, Chelsea & Westminster Hospital, SW10 9NH London, United Kingdom.
authors.forename: G V
authors.initials: GV
authors.lastname: Matthews
authors.forename: D
authors.initials: D
authors.lastname: Pillay
authors.forename: P
authors.initials: P
authors.lastname: Cane
authors.forename: D
authors.initials: D
authors.lastname: Ratcliffe
authors.forename: B
authors.initials: B
authors.lastname: Gazzard
authors.forename: M
authors.initials: M
authors.lastname: Nelson
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000235:genetics; D004359:Drug Therapy, Combination; D000077595:Famciclovir; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006509:Hepatitis B / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D019259:Lamivudine; D015075:2-Aminopurine; D000077595:Famciclovir