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Low-Dose Tenofovir Shows Efficacy in Patients With Lamivudine-Resistant Hepatitis B Virus: Presented at IM
Virologic breakthrough during hepatitis B virus (HBV) treatment with lamivudine is associated with the occurrence of YMDD mutations. Tenofovir disoproxil fumarate (TDF), an inhibitor of viral DNA polymerase approved for HIV therapy, is active against both YMDD+ and wild-type HBV in HIV/HBV co-infections at a dose level of 300 mg, administered once daily (QD).
However, at present there are no dose-finding studies for TDF in HBV-infected patients having the YMDD mutation.
In some individuals with YMDD+ HBV infection, TDF suppresses HBV DNA when administered at a 150 mg QD dose level, researchers reported here at the 2008 Internal Medicine Annual Scientific Meeting (IM).
"This study presents a retrospective analysis of TDF therapy in patients with YMDD+ HBV infections treated at our Hepatology Clinic," explained lead author Anwar Dudekula, MBBS, Associate, Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado.
Dr. Dudekula and colleagues reported their findings here on May 15 in a poster presentation.
With approval from the institutional review board, the investigators collected data on HBV DNA levels, mutational analysis, patient demographics, and standard biochemistries.
Eight patients, 1:1 male to female ratio, with a mean age of 47.5 years (range, 33-67 years), were found to have YMDD+ HBV infection.
Patients were treated with 75 mg to 150 mg dose levels of lamivudine for 1 to 4 years prior to receiving treatment with TDF 150 mg QD. Six patients continued to receive lamivudine concomitant with TDF therapy. Patients were administered TDF therapy for a mean duration of 59 months (range, 46-69 months).
"In 3 patients, DNA was not measurable within 12, 12, and 24 months, respectively, while alanine aminotransferase (ALT) levels normalized by an average of 12 months," noted Dr. Dudekula. Their DNA levels decreased by 3.9 log10 copies/mL after 3 months of therapy, and by 7.1 log10 copies/mL after 12 months.
HBV DNA was quantitated by hybridisation capture or by real-time PCR.
"These 3 patients also had HBVeAb seroconversion at 11, 12, and 52 months after the start of TDF therapy," said Dr. Dudekula.