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拉米夫定耐药相关的 HIV-1 感染者接受含拉米夫定的抗病毒治疗后乙型肝炎病毒耐药。

Hepatitis B virus drug resistance in HIV-1-infected patients taking lamivudine-containing antiretroviral therapy.

机构信息

Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

出版信息

AIDS Patient Care STDS. 2010 Apr;24(4):205-9. doi: 10.1089/apc.2009.0322.

Abstract

A cross-sectional study was conducted in HIV-1-infected patients receiving lamivudine-containing antiretroviral therapy (ART) to determine the prevalence and risk factors of hepatitis B virus drug resistance (HBV-DR). HBV DNA and HBV genotypic resistance test were performed. Patients were categorized into two groups: with and without HBV-DR. There were 84 patients with a mean age (standard deviation [SD]) of 42.2 (10.2) years and 77% were males. Median (range) duration of ART and lamivudine use was 46 (3-177) and 40 (3-140) months, respectively. Median (range) CD4 cell count was 352 (49-790) cells/mm(3). Of all, 19 (23%) had HBV-DR with a median (range) HBV DNA of 2.56 x 10(7) (2.54 x 10(3)-11 x 10(7)) IU/mL. In univariate analysis, there were no differences in age, gender, ART regimen, liver function test, anti-HBc antibody, anti-HCV antibody between the two groups. Patients with HBV-DR had a higher proportion of positive HBeAg (68.4% versus 3.8%, p < 0.001). In multivariate analysis, positive HBeAg (odds ratio [OR) 16.64; 95% confidence interval [CI], 3.31-83.60] and duration of lamivudine use [per 6-month increment, OR 1.24; 95% CI, 1.06-1.36] were significant risk factors for HBV-DR. All 19 patients with HBV-DR had lamivudine resistance with the mutations as follows: M204V/I (95%), L180M/A181T (95%), L80V/I (47%), V173L (32%), and N236T (21%). Of these, 95%, 84%, 84%, and 0% of patients had HBV-DR to telbivudine, entecavir, adefovir, and tenofovir, respectively. HBV-DR is common in HBV/HIV-1 coinfected patients receiving lamivudine-containing ART without tenofovir. Positive HBeAg and longer duration of lamivudine use are risk factors for HBV-DR. In addition to lamivudine resistance, cross-resistance to other anti-HBV drugs is also frequently observed.

摘要

横断面研究在接受含拉米夫定的抗逆转录病毒治疗(ART)的 HIV-1 感染患者中进行,以确定乙型肝炎病毒耐药性(HBV-DR)的流行率和危险因素。进行了 HBV DNA 和 HBV 基因型耐药性检测。患者分为两组:有和没有 HBV-DR。84 例患者的平均年龄(标准差[SD])为 42.2(10.2)岁,77%为男性。ART 和拉米夫定使用的中位(范围)时间分别为 46(3-177)和 40(3-140)个月。中位(范围)CD4 细胞计数为 352(49-790)个细胞/mm³。其中,19 例(23%)有 HBV-DR,HBV DNA 中位数(范围)为 2.56×10⁷(2.54×10³-11×10⁷)IU/mL。在单变量分析中,两组在年龄、性别、ART 方案、肝功能试验、抗 HBc 抗体、抗 HCV 抗体方面无差异。有 HBV-DR 的患者 HBeAg 阳性的比例更高(68.4%比 3.8%,p<0.001)。多变量分析显示,HBeAg 阳性(优势比[OR]16.64;95%置信区间[CI],3.31-83.60)和拉米夫定使用时间(每 6 个月增加,OR 1.24;95%CI,1.06-1.36)是 HBV-DR 的显著危险因素。所有 19 例 HBV-DR 患者均存在拉米夫定耐药,突变如下:M204V/I(95%)、L180M/A181T(95%)、L80V/I(47%)、V173L(32%)和 N236T(21%)。其中,95%、84%、84%和 0%的患者对替比夫定、恩替卡韦、阿德福韦酯和替诺福韦分别有 HBV-DR。HBV-DR 在未使用替诺福韦的接受含拉米夫定的 ART 的 HBV/HIV-1 合并感染患者中很常见。HBeAg 阳性和拉米夫定使用时间较长是 HBV-DR 的危险因素。除拉米夫定耐药外,还经常观察到对其他抗乙型肝炎病毒药物的交叉耐药性。

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