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加蓬HIV阳性患者中广泛的乙型肝炎病毒(HBV)模式、准亚基因型A3和HBV/E的双重循环以及异质性HBV突变

Broad Range of Hepatitis B Virus (HBV) Patterns, Dual Circulation of Quasi-Subgenotype A3 and HBV/E and Heterogeneous HBV Mutations in HIV-Positive Patients in Gabon.

作者信息

Bivigou-Mboumba Berthold, François-Souquière Sandrine, Deleplancque Luc, Sica Jeanne, Mouinga-Ondémé Augustin, Amougou-Atsama Marie, Chaix Marie-Laure, Njouom Richard, Rouet François

机构信息

Laboratoire de Rétrovirologie, Centre International de Recherches Médicales de Franceville (CIRMF), Franceville, Gabon.

Unité Mixte de Recherche VIH et Maladies Infectieuses Associées (UMR-VIH-MIA), CIRMF, Libreville, Gabon.

出版信息

PLoS One. 2016 Jan 14;11(1):e0143869. doi: 10.1371/journal.pone.0143869. eCollection 2016.

Abstract

Integrated data on hepatitis B virus (HBV) patterns, HBV genotypes and mutations are lacking in human immunodeficiency virus type 1 (HIV-1) co-infected patients from Africa. This survey was conducted in 2010-2013 among 762 HIV-1-positive adults from Gabon who were predominantly treated with 3TC-based antiretroviral treatment. HBV patterns were identified using immunoassays detecting total antibody to hepatitis B core antigen (HBcAb), hepatitis B surface antigen (HBsAg), IgM HBcAb, hepatitis B e antigen (HBeAg), antibody to HBsAg (HBsAb) and an in-house real-time PCR test for HBV DNA quantification. Occult hepatitis B (OBI) was defined by the presence of isolated anti-HBc with detectable serum HBV DNA. HBV genotypes and HBV mutations were analyzed by PCR-direct sequencing method. Seventy-one (9.3%) patients tested positive for HBsAg, including one with acute hepatitis B (0.1%; 95% CI, 0.0%-0.2%), nine with HBeAg-positive chronic hepatitis B (CHB) (1.2%; 95% CI, 0.6%-2.2%), 16 with HBeAg-negative CHB (2.1%; 95% CI, 1.2%-3.3%) and 45 inactive HBV carriers (5.9%; 95% CI, 4.4%-7.8%). Sixty-one (8.0%; 95% CI, 6.2%-10.1%) patients showed OBI. Treated patients showed similar HBV DNA levels to those obtained in untreated patients, regardless of HBV patterns. Around 15.0% of OBI patients showed high (>1,000 UI/mL) viremia. The mutation M204V/I conferring resistance to 3TC was more common in HBV/A (47.4%) than in HBV/E isolates (0%) (P = .04). Our findings encouraged clinicians to promote HBV vaccination in patients with no exposure to HBV and to switch 3TC to universal TDF in those with CHB.

摘要

在非洲,关于合并感染1型人类免疫缺陷病毒(HIV-1)患者的乙肝病毒(HBV)模式、HBV基因型和突变的综合数据尚缺。本调查于2010年至2013年期间在加蓬762名HIV-1阳性成人中开展,这些成人主要接受基于拉米夫定(3TC)的抗逆转录病毒治疗。采用免疫测定法检测乙肝核心抗原总抗体(HBcAb)、乙肝表面抗原(HBsAg)、IgM HBcAb、乙肝e抗原(HBeAg)、乙肝表面抗体(HBsAb),并通过内部实时聚合酶链反应(PCR)检测HBV DNA定量,以此确定HBV模式。隐匿性乙型肝炎(OBI)定义为单独存在抗-HBc且血清HBV DNA可检测到。通过PCR直接测序法分析HBV基因型和HBV突变。71例(9.3%)患者HBsAg检测呈阳性,其中1例为急性乙型肝炎(0.1%;95%置信区间,0.0%-0.2%),9例为HBeAg阳性慢性乙型肝炎(CHB)(1.2%;95%置信区间,0.6%-2.2%),16例为HBeAg阴性CHB(2.1%;95%置信区间,1.2%-3.3%),45例为非活动性HBV携带者(5.9%;95%置信区间,4.4%-7.8%)。61例(8.0%;95%置信区间,6.2%-10.1%)患者显示为OBI。无论HBV模式如何,接受治疗的患者与未接受治疗的患者HBV DNA水平相似。约15.0%的OBI患者显示高病毒血症(>1,000 UI/mL)。对3TC耐药的M204V/I突变在HBV/A型中(47.4%)比在HBV/E型分离株中(0%)更常见(P = 0.04)。我们的研究结果鼓励临床医生对未接触过HBV的患者推广HBV疫苗接种,并将CHB患者的3TC换成通用的替诺福韦酯(TDF)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e02a/4713159/acdb80fb3a98/pone.0143869.g001.jpg

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