Our data may have implications for current add-on strategies. (HEPATOLOGY 2009.) Amajor limitation of nucleoside and nucleotide analogues (NA) in hepatitis B virus (HBV) therapy is the selection of HBV resistance variants, which can lead to a rebound in HBV replication and exacerbation of HBV-related disease. HBV polymerase gene variants that mediate HBV resistance are known to confer cross-resistance to other NAs. Today, increasing numbers of patients have experienced NA treatment failure, mostly to lamivudine (LAM) or adefovir dipivoxil (ADV), which poses a growing see more problem for antiviral treatment. Add-on combination therapy with ADV plus LAM was shown to be effective in these patients but only when

initiated during the early stages of resistance development.1 Tenofovir disoproxil fumarate (TDF) was licensed in 2008 for the treatment of HBV infections in Europe and the United States. It has shown antiviral efficacy against a broad spectrum of viral infections, including human immunodeficiency virus (HIV-1) and

HBV infections, and has a decade of use in HIV-1 patients.2 From 2002 onwards, TDF efficacy in HBV therapy was demonstrated in small studies in which the majority of patients had HIV-1 coinfection and in some patients receiving combination therapy with LAM.3–10 TDF is molecularly similar to ADV but can be administered at www.selleckchem.com/products/pexidartinib-plx3397.html higher doses due to its more favorable safety and tolerability profile. Most recently, its strong and lasting antiviral effect was confirmed by two randomized trials in mostly treatment-naïve HBV monoinfected, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients.11 In HIV-1 and HBV infection, TDF has a favorable safety and tolerability profile.12 However, the potential of TDF to treat patients with NA treatment failure

has not yet been systematically studied.5–11In vitro, TDF exerts antiviral efficacy against variants conferring LAM resistance, but possesses some degree of cross-resistance to ADV.13, 14 This retrospective cohort study was therefore conducted to evaluate the effectiveness of TDF monotherapy in treatment-experienced, HBV monoinfected patients with prior LAM and/or ADV failure. ADV, adefovir dipivoxil; Methocarbamol ALT, alanine aminotransferase; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HIV-1, human immunodeficiency virus; LAM, lamivudine; NA, nucleoside/nucleotide analogue; PCR, polymerase chain reaction; TDF, tenofovir disoproxil fumarate. This retrospective cohort study included 16 centers in Germany and one center in the Netherlands. Patients were collected from the Departments of Hepatology and had received TDF monotherapy between 2002 and 2007. Criteria for entering this study were HBV DNA levels ≥4 log10 copies/mL at the initiation of TDF treatment and a minimum period of the TDF therapy of 6 months after failure to a previous NA therapy.