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中国 HIV 和 HBV 合并感染发生率最高的地区,在接受抗逆转录病毒治疗的 HIV/HBV 合并感染患者中,HBV 拉米夫定耐药突变的发生率很高。

High Prevalence of HBV Lamivudine-Resistant Mutations in HBV/HIV Co-Infected Patients on Antiretroviral Therapy in the Area with the Highest Prevalence of HIV/HBV Co-Infection in China.

机构信息

Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis, Nanning, China.

School of Preclinical Medicine, Guangxi Medical University, Nanning, China.

出版信息

Intervirology. 2018;61(3):123-132. doi: 10.1159/000493797. Epub 2018 Oct 26.

Abstract

OBJECTIVES

We aimed to determine the prevalence of hepatitis B virus (HBV) drug-resistant mutations in patients co- infected with HBV/human immunodeficiency virus (HIV), including both drug-naïve subjects and those who received antiretroviral therapy (ART) in Guangxi, where the prevalence of HIV/HBV co-infection is highest in China.

METHODS

Two hundred and three subjects co-infected with HBV/HIV were recruited, including 123 drug-naïve patients (group 1) and 80 who received ART (group 2). The polymerase gene of HBV in the serum of all study subjects was analysed.

RESULTS

The results showed that the prevalence of HBV drug-resistant mutations in group 2 (76.5%, 95% CI 56.3-96.7) was significantly higher than that in group 1 (1.4%, 95% CI -1.4 to 4.2; χ2 = 50.955, p < 0.05). The major pattern of lamivudine (3TC)-resistant mutations is L180M+M204I+L80I (35.7%). In total, 95% of subjects with resistant mutations had cross-resistance to telbivudine and entecavir. No putative tenofovir disoproxil fumarate (TDF) resistance change was found. Five subjects (6.5%) in group 2 had HBV viral loads over 10 × 106 copies/mL. Four of them had 3TC-resistant mutations. Multivariate analysis showed that ART was the only factor associated with the development of drug-resistant mutations.

CONCLUSION

Treating HIV in HIV/HBV co-infection with antiretroviral agents may result in a very high prevalence of HBV 3TC-resistant mutations. TDF could not completely suppress HBV replication.

摘要

目的

本研究旨在确定广西地区乙型肝炎病毒(HBV)/人类免疫缺陷病毒(HIV)共感染患者中,包括初治和已接受抗逆转录病毒治疗(ART)患者中,HBV 耐药突变的流行率。广西是中国 HIV/HBV 共感染率最高的地区。

方法

共招募了 203 例 HBV/HIV 共感染患者,包括 123 例初治患者(组 1)和 80 例接受 ART 治疗的患者(组 2)。对所有研究对象血清中 HBV 聚合酶基因进行分析。

结果

结果显示,组 2(76.5%,95%CI 56.3-96.7)HBV 耐药突变的流行率明显高于组 1(1.4%,95%CI-1.4 至 4.2;χ2=50.955,p<0.05)。拉米夫定(3TC)耐药的主要模式是 L180M+M204I+L80I(35.7%)。共发现 95%的耐药突变对替比夫定和恩替卡韦具有交叉耐药性。未发现替诺福韦酯(TDF)耐药相关改变。组 2 中有 5 例(6.5%)患者的 HBV 病毒载量超过 10×106 拷贝/ml,其中 4 例存在 3TC 耐药突变。多因素分析显示,ART 是耐药突变发生的唯一相关因素。

结论

在 HIV/HBV 共感染中使用抗逆转录病毒药物治疗 HIV 可能导致 HBV 3TC 耐药突变的极高流行率。TDF 不能完全抑制 HBV 复制。

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