Failure of combination therapy with lamivudine and famciclovir following lamivudine monotherapy for hepatitis B virus infection in patients coinfected with human immunodeficiency virus-1

Individuals coinfected with human immunodeficiency virus 1 (HIV-1) and hepa titis B virus (HBV) often receive treatment with an antiretroviral regimen including lamivudine. Lamivudine monotherapy for HBV may lead to drug-resis tant mutations in a significant number of patients. The virological and bio chemical responses of 8 patients coinfected with HBV/HIV-1 treated with bot h lamivudine and famciclovir were studied. Patients exhibiting HBV viral re bound at 1 year were analyzed for the emergence of HBV polymerase mutations . Only 1 patient had no prior exposure to lamivudine. Addition of famciclov ir 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) a t 12 months. The only patient in whom durable viral suppression and HBV e a ntigen seroconversion were noted began receiving lamivudine and famciclovir simultaneously. HBV polymerase gene sequencing identified resistance-assoc iated mutations in 6 of 7 patients with viral rebound. Sequential nucleosid e analogue therapy is unlikely to be successful in achieving long-term supp ression of HBV replication, and combination therapy should be considered at treatment initiation.