Tenofovir for patients with lamivudine-resistant hepatitis B virus (HBV) infection and high HBV DNA level during adefovir therapy.
Incomplete virological response to adefovir dipivoxil (ADV) has been observed in patients with lamivudine-resistant hepatitis B virus (HBV) infection and may be associated with developing resistance and disease progression. We therefore investigated whether the efficacy of viral suppression could be improved by replacing ADV with tenofovir disoproxil fumarate (TDF). Twenty patients with chronic HBV infection (18 HBeAg+), viral breakthrough during lamivudine therapy, and persistent viral replication (>10(4) copies/mL) after 15 months of ADV monotherapy (range 4-28 months) were treated with TDF 300 mg daily and were retrospectively analyzed. A screening for nucleoside/nucleotide analogue resistance mutations within the HBV polymerase gene was performed in all patients by direct sequencing. Within a median of 3.5 months, application of TDF led to undetectable HBV DNA in 19 of 20 patients, as demonstrated by suppression of HBV DNA below the detection limit of 400 copies/mL. Initially elevated ALT levels had normalized in 10 of 14 patients by the end of follow-up (median 12 months, range 3-24 months). Four patients lost HBeAg, after 3, 4, 5, and 16 months, and one patient seroconverted to anti-HBs after 16 months of TDF therapy. Lamivudine-associated mutations (rtV173L, rtL180M, rtM204V/I) could be detected in 6 patients at baseline of TDF, but this obviously did not influence the response. ADV-resistant mutations were not detected. No side effects were reported. In conclusion, these preliminary observations strongly suggest that TDF might be a highly effective rescue drug for HBV-infected patients with altered responsiveness to treatment with lamivudine and ADV.
van Bömmel
Florian
F
Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité-Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany.
Zöllner
Bernhard
B
Sarrazin
Christoph
C
Spengler
Ulrich
U
Hüppe
Dietrich
D
Möller
Bernd
B
Feucht
Heinz-Hubert
HH
Wiedenmann
Bertram
B
Berg
Thomas
T
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D004279:DNA, Viral / Q000235:genetics*; D018450:Disease Progression; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D015684:Gene Products, pol / Q000187:drug effects / Q000235:genetics; D005838:Genotype; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D000068698:Tenofovir; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; D015684:Gene Products, pol; D063065:Organophosphonates; C066027:P protein, Hepatitis B virus; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C053001:adefovir; D000068698:Tenofovir; D000225:Adenine