SEARCH

SEARCH BY CITATION

We thank Dr. Del Poggio and colleagues for their comments outlining their experience in treating hepatitis B e antigen (HBeAg)-negative patients with tenofovir. In their study they showed that even a tenofovir dosage of 75 mg/day was able to induce and maintain virological response in patients with and without genotypic lamivudine-resistant hepatitis B virus (HBV) infection. From this they postulated that a tenofovir escalation study with a dose ranging from 75 to 300 mg/day should be performed, also pointing out that the economic burden of this therapy also justifies such a study.

Analyzing the data presented we only can warn against drawing such far-reaching conclusions. First, there are striking differences regarding the disease activity of the two populations of HBV-infected patients seen in Treviglio and Berlin.1 In our study all lamivudine-resistant patients had high HBV DNA levels (mean, 2.7 × 109 copies/mL), whereas only 1 of the 10 chronically HBV-infected patients from Italy had detectable viremia in the presence of a lamivudine-resistant mutation when he was switched from lamivudine to tenofovir. Second, there is general agreement that early and effective reduction of HBV replication is most important in preventing the selection of drug-resistant mutants.2, 3 Therefore, our observed rapid antiviral effect of tenofovir even in the presence of high viral load is a strong argument in favor of using the safe dose of 300 mg, which in addition may guarantee the prevention of mutants better than dosages of 75 mg. In this respect, our recent observation that we could reduce the viral load even below 6 IU/mL as verified by the more sensitive real-time PCR technology (Cobas TaqMan, Roche Diagnostics Systems, Pleasanton, CA; detection limit 6 IU/mL) in 50% of the tenofovir-treated patients already at week 48 strongly speaks for the use of this kind of tenofovir dosing and the probability to cope effectively even with minimal residual HBV replication (van Bömmel F and Berg T, unpublished data, 2005).

References

  1. Top of page
  • 1
    van Bömmel F, Wünsche T, Mauss S, Reinke P, Bergk A, Schürmann D, et al. Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection. HEPATOLOGY 2004; 40: 1421-1425.
  • 2
    Yuen MF, Sablon E, Hui CK, Yuan HJ, Decraemer H, Lai CL. Factors associated with hepatitis B virus DNA breakthrough in patients receiving prolonged lamivudine therapy. HEPAOLOGY 2001; 34: 785-791.
  • 3
    Germanidis G, Marcellin P, Lau G, Bonino F, Farci P, Hadziyannis S, Jin R, et al. Profound on-treatment viral suppression with peginterferon alfa-2a (40KD) plus lamivudine combination therapy limits the development of YMDD mutations, but does not improve sustained response rates over peginterferon alfa-2a (40kD) alone. HEPATOLOGY 2004; 40(Suppl 1): 653A.

Thomas Berg M.D.*, Florian van Bömmel M.D.*, * Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany