Division of Infectious Diseases, University of California, San Diego, 200 W Arbor Dr, MC 8208, San Diego, CA 92103, USA.
Clin Infect Dis. 2012 Oct;55(8):1135-43. doi: 10.1093/cid/cis612. Epub 2012 Jul 10.
Clinically, human immunodeficiency virus type 1 (HIV-1) pol sequences are used to evaluate for drug resistance. These data can also be used to evaluate transmission networks and help describe factors associated with transmission risk.
HIV-1 pol sequences from participants at 5 sites in the CFAR Network of Integrated Clinical Systems (CNICS) cohort from 2000-2009 were analyzed for genetic relatedness. Only the first available sequence per participant was included. Inferred transmission networks ("clusters") were defined as ≥2 sequences with ≤1.5% genetic distance. Clusters including ≥3 patients ("networks") were evaluated for clinical and demographic associations.
Of 3697 sequences, 24% fell into inferred clusters: 155 clusters of 2 individuals ("dyads"), 54 clusters that included 3-14 individuals ("networks"), and 1 large cluster that included 336 individuals across all study sites. In multivariable analyses, factors associated with being in a cluster included not using antiretroviral (ARV) drugs at time of sampling (P < .001), sequence collected after 2004 (P < .001), CD4 cell count >350 cells/mL (P < .01), and viral load 10,000-100,000 copies/mL (P < .001) or >100,000 copies/mL (P < .001). In networks, women were more likely to cluster with other women (P < .001), and African Americans with other African Americans (P < .001).
Molecular epidemiology can be applied to study HIV transmission networks in geographically and demographically diverse cohorts. Clustering was associated with lack of ARV use and higher viral load, implying transmission may be interrupted by earlier diagnosis and treatment. Observed female and African American networks reinforce the importance of diagnosis and prevention efforts targeted by sex and race.
临床上,人免疫缺陷病毒 1 型(HIV-1)pol 序列用于评估耐药性。这些数据还可用于评估传播网络,并有助于描述与传播风险相关的因素。
对来自 CFAR 网络综合临床系统(CNICS)队列的 5 个地点的 2000-2009 年参与者的 HIV-1 pol 序列进行遗传相关性分析。仅包括每个参与者的第一个可用序列。推断的传播网络(“簇”)定义为具有≤1.5%遗传距离的≥2 个序列。评估包含≥3 名患者的簇(“网络”)的临床和人口统计学关联。
在 3697 个序列中,24%属于推断的簇:155 个 2 人簇(“对”),54 个包含 3-14 个个体的簇(“网络”),以及跨越所有研究地点的 336 个个体的 1 个大簇。在多变量分析中,与聚类相关的因素包括在采样时未使用抗逆转录病毒(ARV)药物(P<.001)、2004 年后采集的序列(P<.001)、CD4 细胞计数>350 个细胞/毫升(P<.01)和病毒载量为 10,000-100,000 拷贝/毫升(P<.001)或>100,000 拷贝/毫升(P<.001)。在网络中,女性更有可能与其他女性聚类(P<.001),非裔美国人更有可能与其他非裔美国人聚类(P<.001)。
分子流行病学可用于研究地理位置和人口统计学上多样化的队列中的 HIV 传播网络。聚类与缺乏 ARV 使用和更高的病毒载量相关,这意味着早期诊断和治疗可能会中断传播。观察到的女性和非裔美国人网络强调了针对性别和种族的诊断和预防工作的重要性。