Relation between chemokine receptor use, disease stage, and HIV-1 subtypes A and D - Results from a rural Ugandan cohort
Relation between chemokine receptor use, disease stage, and HIV-1 subtypes A and D - Results from a rural Ugandan cohort
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DOI：
10.1097/qai.0b013e3180385aa0
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发表时间：
2007-05-01
影响因子：
3.6
通讯作者：
Whitworth, James A. G.
中科院分区：
文献类型：
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作者：
Kaleebu, Pontiano;Nankya, Immaculate L.;Whitworth, James A. G.
目的：为了确定是否有差异，在coreceptor使用受试者感染HIV-1包膜亚型A和D，可以解释这些亚型之间的进展率的差异，在农村乌干达cohol.Methods：HIV-1亚型在env的V3测序或异源双链迁移率测定。辅助受体的使用是由分离株在表达不同辅助受体的U87 CD 4细胞中复制的能力决定的。Fisher精确检验用于检查辅助受体使用与亚型、临床分期和V3电荷之间的关系。Kruskall-Wallis非参数检验用于检查中位CD 4细胞计数、辅助受体使用和亚型之间的相关性。Logistic回归被用来检查预测辅助受体的使用在不同的CD 4 grouping.Results：从66名参与者的分离进行了分析。31例感染A亚型，35例感染D亚型。虽然这项工作是基于一个小的样本量，我们发现统计上的显着差异。在非AIDS临床状态的患者中，D亚型感染者携带X4病毒的概率高于A亚型感染者（Fisher精确检验，P = 0.040）。Logistic回归分析中，我们通过亚型预测X4的使用并通过CD 4组分层，证实了CD 4计数> 200个细胞/μ L的患者中的这些发现（似然比检验，P = 0.003）。与X4或X4/R5相比，R5病毒与更高的中位CD 4细胞计数相关（Kruskall-Wallis检验，P = 0.0045）。V3电荷+5及以上与X4病毒高度相关（Fisher精确检验，P = 0.006）。结论：辅助受体使用的这些亚型差异可能部分解释了我们先前报道的D亚型感染个体与A亚型感染个体相比更快的进展率。我们的观察结果可能会影响未来使用辅助受体抑制剂在这一人群中。
Objectives: To determine whether there are differences in coreceptor use in subjects infected with HIV-1 envelope subtypes A and D that could explain the differences in progression rates between these subtypes in a rural Ugandan cohort.Methods: HIV-1 was subtyped in env by V3 sequencing or heteroduplex mobility assay. Coreceptor use was determined by the ability of the isolates to replicate in U87 CD4 cells expressing different coreceptors. The Fisher exact test was used to examine the relation between coreceptor use and subtype, clinical stage, and V3 charge. The Kruskall-Wallis nonparametric test was used to examine the association between median CD4 cell counts, coreceptor use, and subtype. Logistic regression was used to examine predicted coreceptor use at different CD4 groupings.Results: Isolates from 66 participants were analyzed. Thirty-one were infected with subtype A, and 35 were infected with subtype D. Although this work was based on a small sample size, we found statistically significant differences. The probability of having an X4 virus was higher in subtype D infections than in subtype A infections among those with a non-AIDS clinical status (Fisher exact test, P = 0.040). Logistic regression analysis, in which we predicted X4 use by subtype and stratified by CD4 group, confirmed these findings among those with a CD4 count > 200 cells/mu L (likelihood ratio test, P = 0.003). R5 viruses were associated with higher median CD4 cell counts than X4 or X4/R5 (Kruskall-Wallis test, P = 0.0045). A V3 charge of +5 and greater was highly associated with X4 virus (Fisher exact test, P = 0.006).Conclusions: These subtype differences in coreceptor use may partially explain the faster progression rates we have previously reported in individuals infected with subtype D compared with subtype A. Our observations may have implications for the future use of coreceptor inhibitors in this population.