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喀麦隆西南和滨海地区HIV-1感染患者中乙型肝炎病毒的血清学和基因特征分析

Serologic and genotypic characterization of hepatitis B virus in HIV-1 infected patients from South West and Littoral Regions of Cameroon.

作者信息

Magoro Tshifhiwa, Gachara George, Mavhandu Lufuno, Lum Emmaculate, Kimbi Helen K, Ndip Roland N, Bessong Pascal

机构信息

HIV/AIDS & Global Health Research Program, Department of Microbiology, University of Venda, Private bag X5050, Thohoyandou, 0950, Limpopo, South Africa.

Department of Medical Laboratory Sciences, Kenyatta University, Nairobi, Kenya.

出版信息

Virol J. 2016 Oct 21;13(1):178. doi: 10.1186/s12985-016-0636-x.

Abstract

BACKGROUND

HBV and HIV share similar transmission routes. Concurrent infection with the two viruses usually results in more severe and progressive liver disease, and a higher incidence of cirrhosis, liver cancer and mortality. Further, this co-infection may lead to cross-resistance between HIV and HBV drugs and increased liver injury, either due to direct hepatotoxicity or drug-related immune-reconstitution hepatitis. These challenges necessitate continuous surveillance for HBV among HIV infected individuals to guide patient management. We conducted this study to understand the serologic and genotypic characteristics of HBV among HIV/HBV infected patients in South West and Littoral Regions of Cameroon.

METHODS

Plasma samples were screened for HBsAg, HBeAg, Anti-HBs and anti-HBc using ELISA followed by DNA extraction from all HBsAg positive samples. A 366 bp region covering the overlapping surface/polymerase gene was amplified by a nested PCR and the product sequenced using Big Dye sequencing chemistry. The resulting sequences were then analyzed for genotypes and both escape and drug resistance mutations.

RESULTS

Of the 455 samples in this study, 25.5 % (n = 116) were HBsAg positive and 46 of these had their DNA successfully amplified. Genotype E was found in 32 samples (69.6 %) and genotype A in the rest of the samples. Escape mutations associated with failure of diagnosis (Y100C, R122K and Q129H) and with vaccine escape (Q129R and T131N) were detected in varying frequencies in the population. Polymerase mutations implicated in resistance to lamivudine and other ʟ-nucleoside analogues were detected in seven patients (15.2 %), while all the samples lacked mutations associated with resistance to adefovir and tenofovir.

CONCLUSIONS

These findings suggest the endemicity of HBV and the predominance of genotypes A and E in the study population. Also, drug resistance findings support the use of tenofovir based ART regimens among HIV/HBV co-infected persons. There is need for continuous HBV screening and monitoring in HIV infected individuals in these regions.

摘要

背景

乙肝病毒(HBV)和人类免疫缺陷病毒(HIV)具有相似的传播途径。两种病毒合并感染通常会导致更严重且进展性的肝脏疾病,以及更高的肝硬化、肝癌发病率和死亡率。此外,这种合并感染可能导致HIV和HBV药物之间产生交叉耐药性,并增加肝损伤,这可能是由于直接肝毒性或药物相关的免疫重建性肝炎所致。这些挑战使得有必要对HIV感染者中的HBV进行持续监测,以指导患者管理。我们开展这项研究,旨在了解喀麦隆西南和滨海地区HIV/HBV合并感染患者中HBV的血清学和基因型特征。

方法

采用酶联免疫吸附测定法(ELISA)对血浆样本进行乙肝表面抗原(HBsAg)、乙肝e抗原(HBeAg)、乙肝表面抗体(Anti-HBs)和乙肝核心抗体(anti-HBc)筛查,随后从所有HBsAg阳性样本中提取DNA。通过巢式聚合酶链反应(PCR)扩增覆盖重叠表面/聚合酶基因的366bp区域,并使用大染料测序化学法对产物进行测序。然后对所得序列进行基因型以及逃逸和耐药突变分析。

结果

在本研究的455份样本中,25.5%(n = 116)为HBsAg阳性,其中46份样本的DNA成功扩增。在32份样本(69.6%)中发现E基因型,其余样本为A基因型。在该人群中,检测到与诊断失败相关的逃逸突变(Y100C、R122K和Q129H)以及与疫苗逃逸相关的突变(Q129R和T131N),其出现频率各不相同。在7例患者(15.2%)中检测到与拉米夫定和其他L-核苷类似物耐药相关的聚合酶突变,而所有样本均未检测到与阿德福韦和替诺福韦耐药相关的突变。

结论

这些发现表明HBV在该研究人群中呈地方性流行,且A和E基因型占主导地位。此外,耐药性研究结果支持在HIV/HBV合并感染人群中使用基于替诺福韦的抗逆转录病毒治疗方案。在这些地区,有必要对HIV感染者进行持续的HBV筛查和监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5cc/5073451/0791b30c0d45/12985_2016_636_Fig1_HTML.jpg

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