Amponsah-Dacosta Edina, Rakgole J Nare, Gededzha Maemu P, Lukhwareni Azwidowi, Blackard Jason T, Selabe Selokela G, Mphahlele M Jeffrey
HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa.
HIV and Hepatitis Research Unit, Department of Virology, Sefako Makgatho Health Sciences University and National Health Laboratory Service, MEDUNSA, Pretoria, South Africa; National Health Laboratory Service, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa.
Infect Genet Evol. 2016 Sep;43:232-8. doi: 10.1016/j.meegid.2016.05.035. Epub 2016 May 28.
Reports on the concomitant impact of HIV co-infection and long term highly active anti-retroviral therapy (HAART) on the genetic stability and molecular evolution of HBV are limited in sub-Saharan Africa.
This retrospective study investigated the molecular evolution of chronic HBV in HIV co-infected patients on lamivudine (3TC)-based HAART over a 5year period. Four HIV co-infected patients, consecutively recruited and followed-up, were screened for hepatitis B serological markers, and their viral loads determined. The HBV genome was amplified from longitudinal samples and characterized by Bayesian inference, mutational analysis, and identification of immune selection pressure.
All patients exhibited persistent chronic HBV infection at baseline, as well as over the course of follow-up despite exposure to 3TC-based HAART. The polymerase gene in all isolates was relatively variable prior to HAART initiation at baseline and during the course of follow-up, although primary drug resistance mutations were not detected. All but one patient were infected with HBV subgenotype A1. The divergence rates between baseline and the last follow-up sequences ranged from 0 to 2.0×10(-3) substitutions per site per year (s/s/y). Positive selection pressure was evident within the surface and core genes.
Despite persistent HBV infection in the HIV co-infected patients exposed to long term 3TC-based HAART, the molecular evolution of HBV over a 5year period was unremarkable. In addition, HBV exhibited minimal genetic variability overtime.
在撒哈拉以南非洲地区，关于人类免疫缺陷病毒（HIV）合并感染及长期高效抗逆转录病毒疗法（HAART）对乙型肝炎病毒（HBV）基因稳定性和分子进化的协同影响的报告有限。
这项回顾性研究调查了在基于拉米夫定（3TC）的HAART治疗下，HIV合并感染患者中慢性HBV的分子进化情况，为期5年。连续招募并随访了4名HIV合并感染患者，检测其乙肝血清学标志物，并测定病毒载量。从纵向样本中扩增HBV基因组，并通过贝叶斯推断、突变分析和免疫选择压力鉴定进行特征分析。
所有患者在基线时以及随访期间均表现为持续性慢性HBV感染，尽管接受了基于3TC的HAART治疗。在基线时HAART开始前以及随访期间，所有分离株中的聚合酶基因相对可变，尽管未检测到主要耐药突变。除1名患者外，所有患者均感染了HBV A1亚型。基线与最后一次随访序列之间的分歧率为每年每位点0至2.0×10⁻³个替换（s/s/y）。表面基因和核心基因内存在明显的正选择压力。
尽管接受长期基于3TC的HAART治疗的HIV合并感染患者存在持续性HBV感染，但HBV在5年期间的分子进化并不显著。此外，HBV随时间推移表现出最小的基因变异性。
