Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2011;6(11):e27211. doi: 10.1371/journal.pone.0027211. Epub 2011 Nov 2.
Cross-sectional assessment of HIV incidence relies on laboratory methods to discriminate between recent and non-recent HIV infection. Because HIV diversifies over time in infected individuals, HIV diversity may serve as a biomarker for assessing HIV incidence. We used a high resolution melting (HRM) diversity assay to compare HIV diversity in adults with different stages of HIV infection. This assay provides a single numeric HRM score that reflects the level of genetic diversity of HIV in a sample from an infected individual.
HIV diversity was measured in 203 adults: 20 with acute HIV infection (RNA positive, antibody negative), 116 with recent HIV infection (tested a median of 189 days after a previous negative HIV test, range 14-540 days), and 67 with non-recent HIV infection (HIV infected >2 years). HRM scores were generated for two regions in gag, one region in pol, and three regions in env.
Median HRM scores were higher in non-recent infection than in recent infection for all six regions tested. In multivariate models, higher HRM scores in three of the six regions were independently associated with non-recent HIV infection.
The HRM diversity assay provides a simple, scalable method for measuring HIV diversity. HRM scores, which reflect the genetic diversity in a viral population, may be useful biomarkers for evaluation of HIV incidence, particularly if multiple regions of the HIV genome are examined.
横断面评估 HIV 发病率依赖于实验室方法来区分近期和非近期 HIV 感染。由于 HIV 在感染个体中随时间发生变异,HIV 多样性可作为评估 HIV 发病率的生物标志物。我们使用高分辨率熔解(HRM)多样性测定法比较了不同 HIV 感染阶段的成年人中的 HIV 多样性。该测定法提供了一个单一的 HRM 数值评分,反映了从感染个体样本中 HIV 的遗传多样性水平。
我们测量了 203 名成年人的 HIV 多样性:20 名急性 HIV 感染者(RNA 阳性,抗体阴性),116 名近期 HIV 感染者(上次 HIV 阴性检测后中位数为 189 天,范围 14-540 天),和 67 名非近期 HIV 感染者(HIV 感染>2 年)。对 gag 中的两个区域、pol 中的一个区域和 env 中的三个区域进行了 HRM 评分。
在所有六个测试区域中,非近期感染的 HRM 评分中位数均高于近期感染。在多变量模型中,六个区域中的三个区域的 HRM 评分较高与非近期 HIV 感染独立相关。
HRM 多样性测定法提供了一种简单、可扩展的测量 HIV 多样性的方法。HRM 评分反映了病毒群体中的遗传多样性,可能是评估 HIV 发病率的有用生物标志物,尤其是如果检查 HIV 基因组的多个区域。