在近期诊断感染的患者中存在使用 CXCR4 的 HIV-1:相关性和传播证据。

Presence of CXCR4-using HIV-1 in patients with recently diagnosed infection: correlates and evidence for transmission.

机构信息

AIDS Reference Laboratory, Ghent University, Belgium.

出版信息

J Infect Dis. 2012 Jan 15;205(2):174-84. doi: 10.1093/infdis/jir714. Epub 2011 Dec 5.

Abstract

BACKGROUND

The prevalence and correlates of CXCR4-use in recently diagnosed patients and the impact of X4/DM transmission remain largely unknown.

METHOD

Genotypic coreceptor use determination on the baseline sample of 539 recently diagnosed individuals. Correlation of coreceptor use with clinical, viral and epidemiological data and with information on transmission events as obtained through phylogenetic analysis of protease and reverse transcriptase sequences. Results. CXCR4-use was predicted in 12 to 19% of the patients, depending on the interpretative cutoff used. CXCR4-use was correlated with lower CD4(+) T cell counts and subtype 01_AE infection. No association with viral load was observed. Seven (11%) of 63 transmission clusters and 4 (31%) of 13 donor-source pairs resulted from X4/DM transmission.

CONCLUSION

The results confirmed the relation between CXCR4-use at diagnosis and low baseline CD4+ T cell counts. Significantly more CXCR4-use was predicted in 01_AE infections, which may impose constraints on the use of CCR5 antagonists in certain regions of the world. Observations from the transmission cluster analysis contradict the hypothesis that R5 viruses are selected at transmission, and support the idea that R5 or X4/DM infections result from a stochastic process.

摘要

背景

在最近诊断出的患者中,CXCR4 药物的使用情况及其与 X4/DM 传播的相关性尚不清楚。

方法

对 539 名新诊断个体的基线样本进行基因核心受体使用的测定。将核心受体的使用与临床、病毒和流行病学数据以及通过蛋白酶和逆转录酶序列的系统进化分析获得的传播事件信息进行关联。结果:根据不同的解释性截断值,12%至 19%的患者可预测 CXCR4 药物的使用。CXCR4 药物的使用与较低的 CD4+T 细胞计数和 01_AE 亚型感染有关。未观察到与病毒载量有关。7 个(11%)的 63 个传播簇和 4 个(31%)的 13 个供体-来源对是由 X4/DM 传播引起的。

结论

结果证实了诊断时 CXCR4 药物的使用与基线时 CD4+T 细胞计数低之间的关系。在 01_AE 感染中,预测到的 CXCR4 药物的使用显著增加,这可能对某些地区使用 CCR5 拮抗剂施加了限制。从传播簇分析中得到的观察结果与 R5 病毒在传播中被选择的假设相矛盾,并支持 R5 或 X4/DM 感染是随机发生的观点。

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