Tenofovir (Viread) Effective for Treatment of Chronic Hepatitis B Patients with Suboptimal Response to Adefovir (Hepsera)

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HIV and Hepatitis.com 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.

Results

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.

5/4/10

Reference

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).