Efficacy of tenofovir disoproxil fumarate in the treatment of adults with chronic HBV infection who do not have HIV infection
- Anna SF Lok, MD
Anna SF Lok, MD
- Professor of Medicine
- University of Michigan Medical School
Tenofovir disoproxil fumarate, like adefovir dipivoxil, is a nucleotide reverse transcriptase inhibitor that has activity against the hepatitis B (HBV) and HIV viruses. It is approved for treatment of HIV infection and has also received approval for treatment of chronic HBV.
This topic review will focus on treatment in patients infected with HBV alone. Treatment in patients coinfected with HBV and HIV is presented separately. (See "Treatment of chronic hepatitis B in the HIV-infected patient".)
Tenofovir is an acyclic nucleotide diester analog of adenosine monophosphate, which is administered orally as the prodrug tenofovir disoproxil fumarate (DF) or tenofovir alafenamide. The intracellular, pharmacologically active moiety is tenofovir-diphosphate. Tenofovir DF has been used extensively for the treatment of HIV and chronic hepatitis B virus (HBV) infection. The efficacy of tenofovir DF for the treatment of adults with chronic HBV infection is reviewed below.
A newer formulation of tenofovir, tenofovir alafenamide, is also effective for the treatment of HBV. Two large randomized trials of HBV monoinfected patients found that tenofovir alafenamide was noninferior to tenofovir DF for the treatment of HBV in both treatment-naïve and treatment-experienced hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients, and had fewer adverse effects on renal function and bone density in studies of up to 48 weeks [1,2]. Tenofovir alafenamide (25 mg daily) was approved by the US Food and Drug Administration in November 2016 for the treatment of chronic HBV infection in patients with compensated liver disease .
EFFICACY IN PATIENTS WITH HBeAg-POSITIVE CHRONIC HEPATITIS B
Tenofovir disoproxil fumarate (DF) is effective for the treatment of chronic HBV in patients who are hepatitis B e antigen (HBeAg)-positive. However, patients in the immune tolerant phase of infection should generally not be treated; this issue is discussed elsewhere. (See "Hepatitis B virus: Overview of management", section on 'Indications' and "Hepatitis B virus: Overview of management".)
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- Buti M et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of HBeAg-negative chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial. Lancet Gastroenterol Hepatol 2016 Sep 22;
- U.S. Food and Drug Administration Approves Gilead’s Vemlidy (Tenofovir Alafenamide) for the Treatment of Chronic Hepatitis B Virus Infection. http://www.gilead.com/news/press-releases/2016/11/us-food-and-drug-administration-approves-gileads-vemlidy-tenofovir-alafenamide-for-the-treatment-of-chronic-hepatitis-b-virus-infection (Accessed on November 28, 2016).
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- EFFICACY IN PATIENTS WITH HBeAg-POSITIVE CHRONIC HEPATITIS B
- EFFICACY IN PATIENTS WITH HBeAg-NEGATIVE CHRONIC HEPATITIS B
- RISK OF RESISTANCE
- EFFICACY IN PATIENTS WITH PREVIOUS EXPOSURE TO LAMIVUDINE OR ADEFOVIR
- Lamivudine resistance
- Adefovir resistance
- PATIENTS WITH SPONTANEOUS EXACERBATION
- IN COMBINATION WITH OTHER DRUGS
- Renal insufficiency
- Bone density
- SUMMARY AND RECOMMENDATIONS