HIV-1 Genetic Diversity and Transmitted Drug Resistance Mutations among Patients from the North, Central and South Regions of Angola
HIV-1 Genetic Diversity and Transmitted Drug Resistance Mutations among Patients from the North, Central and South Regions of Angola
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DOI：
10.1371/journal.pone.0042996
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发表时间：
2012-08-29
期刊：
影响因子：
3.7
通讯作者：
Morgado, Mariza G.
中科院分区：
文献类型：
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作者：
Afonso, Joana Morais;Bello, Gonzalo;Morgado, Mariza G.
背景：安哥拉呈现出一种非常复杂的 HIV-1 流行病，其特征是几种 HIV-1 M 亚型、亚型间重组体和未分类 (U) 变体的共同循环。然而，自 2004 年引入 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耐药性突变 (DRM) 的流行情况几乎没有被研究过。 方法：来自安哥拉中部 (n = 44)、北部 (n = 35) 和南部 (n = 22) 地区的 101 名个体被诊断为 HIV-1 阳性，并在 2008 年和 2010 年，在位于罗安达省和本戈省交界处的 Kifangondo 医疗中心，国家艾滋病毒诊断转诊中心之一。基于 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了基因分型，并分析了它们的耐药性概况。结果：在分析的 101 个样本中，51% 聚类为纯 M 亚型，42% 被分类为亚型间重组体，7% 表示为 U。我们观察到不同亚型的患病率存在重要差异。 各国家地区之间的HIV-1遗传变异，北部地区F1亚型频率较高（20%），中部地区亚型间重组频率较高（42%），南部地区C亚型频率较高（45%）。仅在北部与南部 (p = 0.0005) 和中部与南部 (p = 0.0012) 区域之间的 C 亚型患病率中观察到 HIV-1 分支分布存在统计学显着差异。在 16.3% 的分析患者中检测到 DRM 为 NRTI 和/或 NNRTI。 结论：这些结果表明，安哥拉不同地区的 HIV-1 遗传变异分布存在异质性，并且还揭示了在报告未使用抗逆转录病毒药物的患者中，DRM 为 RT 抑制剂的频率出乎意料地高，这可能会降低目前标准一线抗逆转录病毒治疗方案的效率 在国内使用。
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.