Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
AIDS. 2010 May 15;24(8):1177-83. doi: 10.1097/QAD.0b013e328338e4de.
To study transmission dynamics during acute infection, during the aviremic phase over the period of early antiretroviral therapy (ART) and during the phase of viral rebound after early treatment was stopped.
Transmission dynamics was assessed within 111 patients, enrolled in the Zurich primary HIV infection study, by molecular epidemiological methods using pol sequences from genotypic resistance tests and clonal env C2-V3-C3 sequences. Coclustering of Zurich primary HIV infection sequences with 12,303 sequences from 8837 HIV-positive patients enrolled in the multisite Swiss HIV Cohort Study was identified. Furthermore, we investigated transmission patterns within phylogenetic clusters by using longitudinal clinical data and analyzed HIV transmission by stage of infection and attempted to localize transmission events to periods before or after early ART.
Six transmission clusters comprising 20 men having sex with men were identified. Furthermore, linkage to eight men having sex with men from the Swiss HIV Cohort Study could be established. Strikingly, we detected at least five new primary infection events originating from Zurich primary HIV infection patients within 16-61 weeks after stopping early ART. Viral loads of likely index patients varied from 314 up to 1,690,000 HIV-1 RNA copies/ml of plasma at the estimated time of infection.
The large number of new infections originating from men having sex with men who stopped early ART indicates that current preventive efforts are insufficient. In contrast, these patients showed no adherence problems. These findings argue for early, continuous ART in sexually active HIV-1-infected persons not only for individual patient benefits but also specifically to reduce the spread of HIV-1.
研究急性感染期间、早期抗逆转录病毒治疗(ART)期间无病毒血症期以及早期治疗停止后病毒反弹期间的传播动力学。
通过基因耐药测试中的 pol 序列和克隆 env C2-V3-C3 序列的分子流行病学方法,在苏黎世原发性 HIV 感染研究中纳入的 111 名患者中评估了传播动力学。通过对 8837 名 HIV 阳性患者的 12303 个序列和苏黎世原发性 HIV 感染序列进行聚类分析,确定了聚类。此外,我们通过纵向临床数据研究了系统发育簇内的传播模式,并分析了感染阶段的 HIV 传播情况,并试图将传播事件定位在早期 ART 之前或之后的时期。
确定了 6 个包含 20 名男男性接触者的传播簇。此外,还可以确定与瑞士 HIV 队列研究中 8 名男男性接触者的联系。引人注目的是,我们在停止早期 ART 后 16-61 周内检测到至少 5 例源自苏黎世原发性 HIV 感染患者的新原发性感染事件。在估计的感染时间,可能的指数患者的病毒载量在 314 到 1690000 HIV-1 RNA 拷贝/ml 血浆之间变化。
大量新的原发性感染源自停止早期 ART 的男男性接触者,这表明目前的预防措施不足。相比之下,这些患者没有表现出任何服药依从性问题。这些发现表明,为了个体患者的利益,也为了专门减少 HIV-1 的传播,不仅需要在活跃的 HIV-1 感染者中尽早、持续进行 ART。