Viral genetic sequencing can be used to monitor the spread of HIV drug resistance, identify appropriate antiretroviral regimes, and characterize transmission dynamics. Despite decreasing costs, next-generation sequencing (NGS) is still prohibitively costly for routine use in generalized HIV epidemics in low- and middle-income countries. Here, we present veSEQ-HIV, a high-throughput, cost-effective NGS sequencing method and computational pipeline tailored specifically to HIV, which can be performed using leftover blood drawn for routine CD4 cell count testing. This method overcomes several major technical challenges that have prevented HIV sequencing from being used routinely in public health efforts; it is fast, robust, and cost-efficient, and generates full genomic sequences of diverse strains of HIV without bias. The complete veSEQ-HIV pipeline provides viral load estimates and quantitative summaries of drug resistance mutations; it also exploits information on within-host viral diversity to construct directed transmission networks. We evaluated the method’s performance using 1,620 plasma samples collected from individuals attending 10 large urban clinics in Zambia as part of the HPTN 071-2 study (PopART Phylogenetics). Whole HIV genomes were recovered from 91% of samples with a viral load of >1,000 copies/ml. The cost of the assay (30 GBP per sample) compares favorably with existing VL and HIV genotyping tests, proving an affordable option for combining HIV clinical monitoring with molecular epidemiology and drug resistance surveillance in low-income settings.

中文翻译：

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用于低收入环境中艾滋病毒监测和临床监测的综合基因组学解决方案。


病毒基因测序可用于监测艾滋病毒耐药性的传播，确定适当的抗逆转录病毒治疗方案，并表征传播动态。尽管成本不断下降，但在低收入和中等收入国家的普遍艾滋病流行中常规使用下一代测序（NGS）的成本仍然高得令人望而却步。在这里，我们推出了 veSEQ-HIV，这是一种高通量、经济高效的 NGS 测序方法和专门针对 HIV 定制的计算流程，可以使用抽取的剩余血液进行常规 CD4 细胞计数测试。这种方法克服了阻碍艾滋病毒测序在公共卫生工作中常规使用的几个主要技术挑战；它快速、强大且经济高效，并且可以无偏见地生成不同 HIV 毒株的完整基因组序列。完整的 veSEQ-HIV 管道提供病毒载量估计和耐药突变的定量总结；它还利用宿主内病毒多样性的信息来构建定向传播网络。作为 HPTN 071-2 研究（PopART 系统发育学）的一部分，我们使用从赞比亚 10 个大型城市诊所就诊的个人收集的 1,620 个血浆样本评估了该方法的性能。从 91% 的样本中回收了整个 HIV 基因组，病毒载量为 >1,000 拷贝/ml。该检测的成本（每个样本 30 英镑）与现有的 VL 和 HIV 基因分型检测相比毫不逊色，为低收入环境中将 HIV 临床监测与分子流行病学和耐药性监测相结合提供了一种经济实惠的选择。