Investigation of mutations in the partial sequences of the surface and polymerase genes of hepatitis B virus associated with immune escape and drug resistance in HIV-infected patients.

Q2 Pharmacology, Toxicology and Pharmaceutics

F1000Research Pub Date : 2025-08-21 eCollection Date: 2023-01-01 DOI:10.12688/f1000research.132498.4

Lorato Modise, Nomathamsanqa Sithebe, Hazel Mufhandu

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引用次数: 0

Abstract

Background: Co-infection of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) has an impact on high HBV replication and progression to liver cancer. These may lead to cross-resistance of drugs due to natural mutations or therapeutic pressure. These require continuous monitoring of HBV variants for better diagnosis and treatment strategies.

Methods: Convenience sampling was used to collect fifty archival sera from Inkosi Albert Luthuli Central Hospital. Sera were subjected to HBsAg screening using ELISA, DNA extraction, PCR amplification, Sanger sequencing, genotype prediction and mutation analysis.

Results: Of the 50 samples, 86% (43/50) were HBsAg positive; 82% (41/50) PCR positive with 92% (38/41) sequenced and only 26 sequences were subjected to molecular characterization. The HBV sequences showed similarity to genotype A (73% [19/26]), genotypes G (5% [3/26]) and genotype C (15% [4/26]). Prevalence of the mutations in the surface region was (47% [18/38]); including diagnostic failure (K122R and T143S) and immune escape mutations (P127T, G145R, S207N, Y200T, E164D, Y206H and L209V). The mutations in the RT were at (36% [14/38]) with drug resistance mutations (DRM) at (50% [7/14]). Mutations showed resistance to lamivudine (LMV) at (35% [5/14]), telbivudine (LdT) at (29% [4/14]), (14% [2/14]) for entecavir (ETV) and (21% [3/14]) for adefovir (ADV). One sample had a combination of L180M, M204V, S202K, and M250I mutations.

Conclusions: Our findings highlight the prevalence of HBV genotype A in HIV-infected patients in South Africa. The study provides evidence of mutations linked to immune evasion and drug resistance; this infers that these mutations may have clinical implications for the diagnosis and treatment of HBV in HBV/HIV co-infected individuals. Further in vitro studies must be conducted to explore the impact of the identified mutation on the surface protein expression during diagnosis; phenotype impact of the mutant virus towards the antiviral drugs.

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乙型肝炎病毒突变与人类免疫缺陷病毒感染患者免疫逃逸和耐药相关的研究。

背景：乙型肝炎病毒（HBV）和人类免疫缺陷病毒（HIV）的联合感染对HBV高复制和肝癌进展有影响。由于自然突变或治疗压力，这些可能导致药物的交叉耐药。这需要持续监测HBV变异，以获得更好的诊断和治疗策略。方法：采用方便抽样法采集50份卢图利中心医院档案血清。采用ELISA、DNA提取、PCR扩增、Sanger测序、基因型预测和突变分析对血清进行HBsAg筛选。结果：50例样本中，86% (N= 43/50) HBsAg阳性；82% (N=41/50) PCR阳性，92% （N=38/41）测序，仅有26个序列进行了分子鉴定。HBV序列与基因型A （73% [N=19/26]）、基因型G （5% [N=3/26]）和基因型c （15% [N=4/26]）相似。表面区突变发生率为47% [N=18/38]；包括诊断失败（K122R和T143S）和免疫逃逸突变（P127T、G145R、S207N、Y200T、E164D、Y206H和L209V）。RT突变（36% [N=14/38]），耐药突变（DRM）（50%[7/14]）。突变显示对恩替卡韦（ETV）和阿德福韦（ADV）的耐药分别为拉米夫定（LMV）（35%[5/14]）、替比夫定（LdT）（29%[4/14]）和（14%[2/14]）（21%[3/14]）。其中一个样本有L180M、M204V、S202K和M250I的组合突变。结论：我们的研究结果强调了南非hiv感染患者中HBV基因型A的患病率。该研究提供了与免疫逃避和耐药性有关的突变的证据；这推断这些突变可能对HBV/HIV合并感染个体的HBV诊断和治疗具有临床意义。在诊断过程中，必须进行进一步的体外研究，以探索所鉴定的突变对表面蛋白表达的影响；突变病毒对抗病毒药物的表型影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

F1000Research Pharmacology, Toxicology and Pharmaceutics-Pharmacology, Toxicology and Pharmaceutics (all)

CiteScore

5.00

自引率

0.00%

发文量

1646

审稿时长

1 weeks

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