Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection.

Abstract

BACKGROUND:

Long-term tenofovir disoproxil fumarate (TDF) treatment for chronic hepatitis B (CHB) is associated with sustained viral suppression and regression of fibrosis and cirrhosis at year 5 (240 weeks) and no TDF resistance through 6 years (288 weeks).

AIM:

We assessed the efficacy, safety, and resistance of TDF for up to 7 years (336 weeks) in HBeAg-positive and HBeAg-negative CHB patients.

METHODS:

Patients who completed 1 year (48 weeks) of randomized treatment with TDF or adefovir dipivoxil were eligible to receive open-label TDF for a total duration of 8 years (384 weeks).

RESULTS:

Of 641 patients initially randomized, 585 (91.3 %) entered the open-label phase; 437/585 (74.7 %) remained on study at year 7. For patients on treatment at year 7, 99.3 % maintained viral suppression (HBV DNA < 69 IU/mL), 80.0 % achieved serum alanine aminotransferase normalization, and in HBeAg-positive patients, 84/154 (54.5 %) and 25/154 (11.8 %) achieved HBeAg and HBsAg loss, respectively. One/375 (0.3 %) HBeAg-negative patients achieved HBsAg loss. No resistance to TDF was detected through 7 years. During the open-label phase, grade 3/4 drug-related adverse events were uncommon (1.0 %); ten (1.7 %) patients had elevation of serum creatinine ≥ 0.5 mg/dL above baseline. No significant change in bone mineral density was observed from year 4 to year 7 (week 192 to week 336).

CONCLUSIONS:

Long-term TDF treatment was associated with sustained virologic, biochemical, and serologic responses, without resistance. TDF treatment was well tolerated, with a low incidence of renal and bone events. These data confirm the safety and efficacy of long-term TDF for CHB.

• Authors: Maria Buti, Naoky Tsai, Joerg Petersen, Robert Flisiak, Selim Gurel, Zahary Krastev, Raul Aguilar Schall, John F Flaherty, Eduardo B Martins, Prista Charuworn, Kathryn M Kitrinos, G Mani Subramanian, Edward Gane, Patrick Marcellin
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 60 Issue 5 Pg. 1457-64 (05 2015) ISSN: 1573-2568 [Electronic] United States
• PMID: 25532501 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• 9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine
• Antiviral Agents
• Biomarkers
• DNA, Viral
• Hepatitis B e Antigens
• Phosphorous Acids
• Adenine

Topics

• Adenine (administration & dosage, adverse effects, analogs & derivatives)
• Antiviral Agents (administration & dosage, adverse effects)
• Biomarkers (blood)
• DNA, Viral (blood)
• Drug Administration Schedule
• Drug Resistance, Viral
• Hepatitis B e Antigens (blood)
• Hepatitis B virus (drug effects, genetics, immunology)
• Hepatitis B, Chronic (diagnosis, drug therapy)
• Humans
• Phosphorous Acids (administration & dosage, adverse effects)
• Time Factors
• Treatment Outcome
• Viral Load