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HIV and Coverage of the
45th Annual Meeting of the European
Association for the Study of the Liver (EASL 2010)

April 14 - 18, 2010, Vienna, Austria
Tenofovir (Viread) Effective for Treatment of Chronic Hepatitis B Patients with Suboptimal Response to Adefovir (Hepsera)

SUMMARY: Treatment with tenofovir (Viread) monotherapy for up to 96 weeks produced complete suppression of hepatitis B virus (HBV) in patients who had detectable viral load using the related nucleotide analog adefovir (Hepsera), according to data from a pooled analysis presented at the 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010) last month in Vienna. In addition, tenofovir was well tolerated and no drug resistance was observed.

By Liz Highleyman

M. Manns from Medizinische Hochschule in Hannover, Germany, and an international team of colleagues evaluated the activity of tenofovir in patients with suboptimal virological response (HBV DNA remained > 400 copies/mL) to adefovir, with or without prior use of lamivudine (Epivir-HBV).

Tenofovir has demonstrated potent activity in hepatitis B "e" antigen (HBeAg) positive and negative, treatment-nave and lamivudine-experienced chronic hepatitis B patients, the researchers noted as background. But in vitro studies have shown varying degrees of sensitivity to tenofovir in virus strains with different patterns of adefovir-associated resistance mutations.

This retrospective pooled analysis included 160 HBeAg positive and HBeAg negative patients with persistent viral replication after at least 24 weeks (mean 53 weeks) of adefovir therapy; 23% also had prior lamivudine experience. Participants were treated with tenofovir for up to 96 weeks in 3 randomized Gilead studies: GS-US-174-0102 (35 patients), GS-US-174-0103 (72 patients), and GS-US-174-0106 (53 patients).

A majority of participants (approximately 75%), were men, roughly half were white, and about one-third were Asian, though proportions differed considerably from study to study. Overall, 65% were HBeAg positive; about 43% had HBV genotype D, 36% had genotype C, 19% had genotype A, and 9% had genotype B.

Studies 102 (HBeAg negative) and 103 (HBeAg positive) compared tenofovir vs adefovir for 48 weeks, followed by open-label tenofovir through 96 weeks. Study 106 compared tenofovir monotherapy vs tenofovir plus emtricitabine (Emtriva) in adefovir-resistant patients. Participants with HBV DNA > 400 copies/mL after week 24 could choose to add emtricitabine; they were considered to have treatment failure if the combination still did not suppress viral replication.


Overall, in an intent-to-treat analysis, 77% of patients in the 3 trials had HBV DNA < 400 copies/mL after 24 weeks of tenofovir monotherapy:
75% of 141 participants with no baseline resistance mutations;
86% of 7 patients with lamivudine resistance;
83% of 12 patients with adefovir resistance.
59% of participants had normalized alanine aminotransferase (ALT), and indicator of liver inflammation, at week 24.
These responses were maintained through 96 weeks of treatment.
Among the 104 HBeAg positive patients, 10% experienced HBeAg loss and 7% experienced HBeAg seroconversion during year 1, and 15% and 10%, respectively, did so during year 2.
Tenofovir was generally well-tolerated.
No participants discontinued therapy early due to an adverse event.
2 patients experienced serious adverse events considered related to tenofovir.
2 patients experienced a 0.5 mg/dL increase in creatinine -- an indicator of kidney impairment -- but remained on tenofovir following dose reduction.
No participants experienced a decrease in creatinine clearance to < 50 mL/min.
No mutations associated with tenofovir resistance emerged through 96 weeks.

"Complete viral suppression was observed following up to 96 weeks of tenofovir monotherapy in the majority of patients with incomplete viral suppression on adefovir, including those with prior lamivudine use," the investigators concluded. "The safety and tolerability profile of tenofovir was good and no resistance to tenofovir was observed."

Medizinische Hochschule Hannover, Hannover, Germany; University of Toronto, Toronto, Ontario, Canada; Hopital Beaujon, Clichy, France; Medizinische Klink mit Schwerpunkt, Humboldt-Universität, Berlin, German; Gilead Sciences, Inc, Durham, NC.


M Manns, J Heathcote, P Marcellin, and others. Efficacy of tenofovir DF treatment in patients with a suboptimal response to adefovir dipivoxil. 45th Annual Meeting of the European Association for the Study of the Liver (EASL 2010). Vienna, Austria. April 14-18, 2010. (Abstract 1017).