Tenofovir disoproxil fumarate for the treatment of lamivudine-resistant hepatitis B.
OBJECTIVE
Lamivudine resistance occurs in patients with chronic hepatitis B at rates of 16%-32% after 1 year and 49% after 3 years. Adefovir dipivoxil, a nucleotide analogue recently approved by the Food and Drug Administration for the treatment of chronic hepatitis B, is effective against hepatitis B virus (HBV) but has been associated with renal toxicity at high doses. Tenofovir disoproxil fumarate is another nucleotide analogue with demonstrated antiviral activity against both wild-type and lamivudine-resistant HBV. Tenofovir, at its licensed dose, has not been associated with renal dysfunction.


METHODS
We describe a series of 9 patients with lamivudine-resistant hepatitis B treated with tenofovir, 300 mg, once daily before the availability of adefovir. Levels of HBV DNA, alanine aminotransferase (ALT), hepatitis B e antigen (HBeAg), and antibody to HBeAg (anti-HBe) were monitored.


RESULTS
The addition of tenofovir to the existing regimen of lamivudine resulted in a median decline of 4.5 log(10) copies/mL in HBV DNA levels (range, 3.2-6.3 log(10) copies/mL) after a median treatment duration of 12 months (range, 6-16 mo). HBeAg seroconversion was observed in 2 patients, with a third patient undergoing HBeAg loss while remaining anti-HBe negative. In 4 of 7 patients with elevated ALT levels at baseline, ALT levels normalized. No significant adverse events were encountered during treatment.


CONCLUSIONS
In patients with lamivudine-resistant hepatitis B, treatment with tenofovir is well tolerated and results in significant virological, serological, and biochemical improvements on par with those seen with high-dose adefovir (30 mg/day) therapy, without the complication of renal toxicity.
Kuo
Alexander
A
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetss 02114, USA.
Dienstag
Jules L
JL
Chung
Raymond T
RT
D000225:Adenine / Q000008:administration & dosage* / Q000031:analogs & derivatives; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D018570:Risk Assessment; D012494:Sampling Studies; D012720:Severity of Illness Index; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load
D063065:Organophosphonates; D009943:Organophosphorus Compounds; D019259:Lamivudine; D000068698:Tenofovir; D000225:Adenine