Van Zyl Gert U, Katusiime Mary Grace, Wiegand Ann, McManus William R, Bale Michael J, Halvas Elias K, Luke Brian, Boltz Valerie F, Spindler Jonathan, Laughton Barbara, Engelbrecht Susan, Coffin John M, Cotton Mark F, Shao Wei, Mellors John W, Kearney Mary F
Division of Medical Virology, Stellenbosch University and National Health Laboratory Service (NHLS) Tygerberg, Cape Town, South Africa.
HIV Dynamics and Replication Program, National Cancer Institute (NCI), Frederick, Maryland, USA.
J Clin Invest. 2017 Oct 2;127(10):3827-3834. doi: 10.1172/JCI94582. Epub 2017 Sep 11.
It remains controversial whether current antiretroviral therapy (ART) fully suppresses the cycles of HIV replication and viral evolution in vivo. If replication persists in sanctuary sites such as the lymph nodes, a high priority should be placed on improving ART regimes to target these sites. To investigate the question of ongoing viral replication on current ART regimens, we analyzed HIV populations in longitudinal samples from 10 HIV-1-infected children who initiated ART when viral diversity was low. Eight children started ART at less than ten months of age and showed suppression of plasma viremia for seven to nine years. Two children had uncontrolled viremia for fifteen and thirty months, respectively, before viremia suppression, and served as positive controls for HIV replication and evolution. These latter 2 children showed clear evidence of virus evolution, whereas multiple methods of analysis bore no evidence of virus evolution in any of the 8 children with viremia suppression on ART. Phylogenetic trees simulated with the recently reported evolutionary rate of HIV-1 on ART of 6 × 10-4 substitutions/site/month bore no resemblance to the observed data. Taken together, these data refute the concept that ongoing HIV replication is common with ART and is the major barrier to curing HIV-1 infection.
目前的抗逆转录病毒疗法（ART）是否能在体内完全抑制HIV复制和病毒进化的周期仍存在争议。如果在淋巴结等庇护所部位持续存在复制，那么应高度优先改进ART方案以靶向这些部位。为了研究当前ART方案下病毒是否持续复制的问题，我们分析了10名HIV-1感染儿童的纵向样本中的HIV群体，这些儿童在病毒多样性较低时开始接受ART治疗。8名儿童在不到10个月大时开始接受ART治疗，并在7至9年的时间里血浆病毒血症得到抑制。2名儿童在病毒血症抑制之前分别有15个月和30个月的病毒血症未得到控制，作为HIV复制和进化的阳性对照。后两名儿童显示出明显的病毒进化证据，而多种分析方法均未发现8名接受ART治疗后病毒血症得到抑制的儿童中有任何病毒进化的证据。用最近报道的HIV-1在ART治疗下的进化速率6×10-4替换/位点/月模拟的系统发育树与观察到的数据毫无相似之处。综上所述，这些数据反驳了以下观点，即接受ART治疗时HIV持续复制很常见，并且是治愈HIV-1感染的主要障碍。
