Presence of CXCR4-Using HIV-1 in Patients With Recently Diagnosed Infection: Correlates and Evidence for Transmission
Presence of CXCR4-Using HIV-1 in Patients With Recently Diagnosed Infection: Correlates and Evidence for Transmission
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DOI：
10.1093/infdis/jir714
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发表时间：
2012-01-15
影响因子：
6.4
通讯作者：
Verhofstede, Chris
中科院分区：
文献类型：
--
作者：
Chalmet, Kristen;Dauwe, Kenny;Verhofstede, Chris
背景资料。新近确诊的患者中使用CXCR4的患病率和相关性以及X4/DM传播的影响在很大程度上仍不清楚。539例新近确诊的个体的基线样本中的基因型协受体使用测定。辅受体的使用与临床、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发育分析获得的传播事件信息的相关性。12%到19%的患者预测到CXCR4的使用，这取决于使用的解释性截断值。CXCR4的使用与低CD4(+)T细胞计数和01_AE亚型感染相关。没有观察到与病毒载量有关。63个传播群中的7个(11%)和13个供源对中的4个(31%)来自X4/DM传播。这一结果证实了CXCR4在诊断时的使用与低基线CD4+T细胞计数的关系。在01_AE感染中，预计会有更多的CXCR4使用，这可能会限制CCR5拮抗剂在世界某些地区的使用。传播聚类分析的观察结果与R5病毒在传播时被选择的假设相矛盾，并支持R5或X4/DM感染是一个随机过程的观点。
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.