González-Domenech Carmen M, Viciana Isabel, Delaye Luis, Mayorga María Luisa, Palacios Rosario, de la Torre Javier, Jarilla Francisco, Castaño Manuel, Del Arco Alfonso, Clavijo Encarnación, Santos Jesús
Biomedical Research Institute of Malaga (IBIMA), Málaga, Spain.
Infectious Diseases and Clinical Microbiology Unit, Virgen de la Victoria Hospital, Málaga, Spain.
PLoS One. 2018 Jan 8;13(1):e0190544. doi: 10.1371/journal.pone.0190544. eCollection 2018.
CRF19_cpx is a complex circulating recombination form (CRF) of HIV-1. We describe the characteristics of an outbreak of the CRF19_cpx variant among treatment-naïve patients in southern Spain.
The study was undertaken at the Virgen de la Victoria Hospital, a reference centre for the analysis of HIV-1 genotype in Malaga (Spain). Subtyping was performed through REGA v3.0 and the relationship of our CRF19_cpx sequences, among themselves and regarding other reference sequences from the same variant, was defined by phylogenetic analysis. We used PhyML program to perform a reconstruction of the phylogeny by Maximum Likelihood method as well as further confirmation of the transmission clusters by Bayesian inference. Additionally, we collected demographic, clinical and immunovirological data.
Between 2011 and 2016, we detected 57 treatment-naïve patients with the CRF19_cpx variant. Of these, 55 conformed a very well-defined transmission cluster, phylogenetically close to CRF19_cpx sequences from the United Kingdom. The origin of this subtype in Malaga was dated between 2007 and 2010. Over 50% of the patients presented the non-nucleoside reverse transcriptase inhibitor G190A resistance mutation. This variant was mostly represented by young adult Spanish men who had sex with men. Almost half of them were recent seroconverters, though a similar percentage was diagnosed at a late state of HIV infection. Five cases of AIDS and one non-AIDS defined death occurred during follow-up. The majority of patients treated with first-line combination antiretroviral therapy (ART) responded.
We report the largest HIV-1 CRF19_cpx cohort of treatment-naïve patients outside Cuba, almost all emerging as an outbreak in the South of Spain. Half the cases had the G190A resistance mutation. Unlike previous studies, the variant from Malaga seems less pathogenic, with few AIDS events and an excellent response to ART.
CRF19_cpx是HIV-1的一种复杂循环重组形式(CRF)。我们描述了西班牙南部初治患者中CRF19_cpx变体的暴发特征。
该研究在西班牙马拉加的维森德拉克维多利亚医院进行,该医院是HIV-1基因型分析的参考中心。通过REGA v3.0进行亚型分型,并通过系统发育分析确定我们的CRF19_cpx序列之间以及与来自同一变体的其他参考序列之间的关系。我们使用PhyML程序通过最大似然法进行系统发育重建,并通过贝叶斯推断进一步确认传播簇。此外,我们收集了人口统计学、临床和免疫病毒学数据。
2011年至2016年期间,我们检测到57例携带CRF19_cpx变体的初治患者。其中,55例构成了一个定义明确的传播簇,在系统发育上与来自英国的CRF19_cpx序列接近。该亚型在马拉加的起源时间为2007年至2010年。超过50%的患者存在非核苷类逆转录酶抑制剂G190A耐药突变。该变体主要见于与男性发生性行为的年轻西班牙男性。其中近一半是近期血清转化者,不过相似比例的患者在HIV感染晚期被诊断出来。随访期间发生了5例艾滋病病例和1例非艾滋病定义的死亡。大多数接受一线联合抗逆转录病毒治疗(ART)的患者有反应。
我们报告了古巴以外最大的初治HIV-1 CRF19_cpx队列,几乎所有病例都在西班牙南部暴发。半数病例有G190A耐药突变。与先前的研究不同,马拉加的变体似乎致病性较低,艾滋病事件较少,对ART反应良好。