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安哥拉北部、中部和南部地区患者的 HIV-1 遗传多样性和传播耐药性突变。

HIV-1 genetic diversity and transmitted drug resistance mutations among patients from the North, Central and South regions of Angola.

机构信息

Laboratorio de AIDS & Imunologia Molecular, Instituto Oswaldo Cruz-FIOCRUZ, Rio de Janeiro, Brazil.

出版信息

PLoS One. 2012;7(8):e42996. doi: 10.1371/journal.pone.0042996. Epub 2012 Aug 29.

Abstract

BACKGROUND

Angola presents a very complex HIV-1 epidemic characterized by the co-circulation of several HIV-1 group M subtypes, intersubtype recombinants and unclassified (U) variants. The viral diversity outside the major metropolitan regions (Luanda and Cabinda) and the prevalence of transmitted drug resistance mutations (DRM) since the introduction of HAART in 2004, however, has been barely studied.

METHODS

One hundred and one individuals from the Central (n = 44), North (n = 35), and South (n = 22) regions of Angola were diagnosed as HIV-1 positive and had their blood collected between 2008 and 2010, at one of the National Referral Centers for HIV diagnosis, the Kifangondo Medical Center, located in the border between the Luanda and Bengo provinces. Angolan samples were genotyped based on phylogenetic and bootscanning analyses of the pol (PR/RT) gene and their drug resistance profile was analyzed.

RESULTS

Among the 101 samples analyzed, 51% clustered within a pure group M subtype, 42% were classified as intersubtype recombinants, and 7% were denoted as U. We observed an important variation in the prevalence of different HIV-1 genetic variants among country regions, with high frequency of subtype F1 in the North (20%), intersubtype recombinants in the Central (42%), and subtype C in the South (45%). Statistically significant difference in HIV-1 clade distribution was only observed in subtype C prevalence between North vs South (p = 0.0005) and Central vs South (p = 0.0012) regions. DRM to NRTI and/or NNRTI were detected in 16.3% of patients analyzed.

CONCLUSIONS

These results demonstrate a heterogeneous distribution of HIV-1 genetic variants across different regions in Angola and also revealed an unexpected high frequency of DRM to RT inhibitors in patients that have reported no antiretroviral usage, which may decrease the efficiency of the standard first-line antiretroviral regimens currently used in the country.

摘要

背景

安哥拉的 HIV-1 疫情非常复杂,其特征是存在多种 HIV-1 M 组亚型、亚型间重组体和未分类(U)变体的共同循环。然而,在 2004 年引入高效抗逆转录病毒治疗(HAART)以来,主要大都市地区(罗安达和卡宾达)以外的病毒多样性以及传播的耐药突变(DRM)的流行情况几乎没有得到研究。

方法

2008 年至 2010 年间,在位于罗安达和本戈省边界的国家艾滋病毒诊断参考中心之一——基方东医疗中心,对来自安哥拉中部(n=44)、北部(n=35)和南部(n=22)地区的 101 名被诊断为 HIV-1 阳性的个体进行了血液采集。根据 pol(PR/RT)基因的系统发育和引导扫描分析对安哥拉样本进行基因分型,并分析其耐药谱。

结果

在分析的 101 个样本中,51%聚类为纯 M 组亚型,42%分类为亚型间重组体,7%为 U 型。我们观察到不同国家地区 HIV-1 遗传变异的流行率存在重要差异,北部(20%)高度流行 F1 亚型,中部(42%)为亚型间重组体,南部(45%)为 C 亚型。仅在北 vs 南(p=0.0005)和中 vs 南(p=0.0012)地区观察到 HIV-1 支系分布的统计学显著差异,即 C 亚型的流行率。在分析的患者中,16.3%检测到对 NRTI 和/或 NNRTI 的耐药突变。

结论

这些结果表明,HIV-1 遗传变异在安哥拉不同地区的分布存在异质性,并且还显示出出乎意料的高频率对 RT 抑制剂的耐药突变,而这些患者报告没有使用抗逆转录病毒药物,这可能降低该国目前使用的标准一线抗逆转录病毒方案的效率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f57/3430682/cc75f85041de/pone.0042996.g001.jpg

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