阿地治疗反应不佳或耐药患者用特纳福韦可快速降低HBV-DNA病毒水平(56 AASLD)

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Treatment with Tenofovir Results in a Rapid Decrease of HBV-DNA Viral Load in Patients with Resistance or Sub-optimal Response to Adefovir

Adefovir dipivoxil [Hepsera] has demonstrated activity against lamivudine [Epivir-HBV]- resistant strains of hepatitis B virus (HBV). However, the N236T mutation in domain D of the hepatitis B virus (HBV) polymerase is associated with phenotypic resistance to adefovir [Hepsera].

In vitro data suggest that the N236T mutant exhibits only a 4.5 fold decrease in sensitivity to tenofovir. J Villeneuve and colleagues at CHUM - H魀ital Saint-Luc in LACE w:st="on">Montreal, CanadaLACE> therefore examined the efficacy of tenofovir in patients with adefovir resistance.

[They] also explored the usefulness of tenofovir in patients with suboptimal response to adefovir, but without genotypic resistance.

Two patients who were receiving adefovir because of lamivudine resistance developed resistance to adefovir, after 36 and 12 months of treatment respectively.

The first case was receiving lamivudine + adefovir and the second case adefovir monotherapy. The N236T mutation of the HBV-polymerase was demonstrated by the INNO-LiPA test (HBV DR v2, Innogenetics).

They were treated with tenofovir 300mg id plus lamivudine 100mg id and adefovir was stopped. Four additional patients without genotypic resistance, but with sub-optimal response to adefovir were also switched to tenofovir 300mg id.

They were also receiving adefovir + lamivudine because of lamivudine resistance. These 4 cases had HBV-DNA viral loads of 97 x 106, 42 x 106, 14 x 106 and 3.6 x 106 millions copies/ml after 13, 23, 29 and 25 months of treatment with adefovir respectively.

HBV-DNA viral loads were measured by the Bayer b-DNA assay (lower limit of detection = 2000 copies/ml).

Results

• The two patients with resistance to adefovir showed a good response to tenofovir.
• In the first case, serum HBV-DNA decreased from 93 x 106 copies/ml at baseline to 9,300 copies/ml after 6 months of treatment with tenofovir.
• In the second patient, serum HBV-DNA decreased from > 100 x 106 copies/ml at baseline to 23,000 copies/ml after 7 months of treatment.
• In the 4 patients with sub-optimal response to adefovir, tenofovir treatment produced a > 1 log drop in viral load after 1 month and a > 2 log drop after 3 months of therapy.

[The authors conclude], 揟reatment with tenofovir induces a rapid decrease of HBV-DNA viral load in patients with resistance or sub-optimal response to adefovir.?/span>

11/16/05

Reference
J Villeneuve and others. Efficacy of Tenofovir in Patients with Chronic Hepatitis B and Resistance or Sub-optimal Response to Adefovir. Abstract 997. Program and Abstracts of the 56^th annual meeting of the American Association for the Study of Liver Diseases. November 11-15, 2005. LACE w:st="on">San Francisco, CALACE>.

[此贴子已经被作者于2005-11-16 16:24:04编辑过]