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No evidence of HIV replication in children on antiretroviral therapy
The Journal of Clinical Investigation ( IF 13.3 ) Pub Date : 2017-09-11 , DOI: 10.1172/jci94582
Gert U Van Zyl 1 , Mary Grace Katusiime 1 , Ann Wiegand 2 , William R McManus 2 , Michael J Bale 2 , Elias K Halvas 3 , Brian Luke 4 , Valerie F Boltz 2 , Jonathan Spindler 2 , Barbara Laughton 5 , Susan Engelbrecht 1 , John M Coffin 6 , Mark F Cotton 5 , Wei Shao 4 , John W Mellors 3 , Mary F Kearney 2
Affiliation  

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.

中文翻译:


没有证据表明接受抗逆转录病毒治疗的儿童体内存在艾滋病毒复制



目前的抗逆转录病毒疗法(ART)是否完全抑制体内HIV复制和病毒进化的周期仍存在争议。如果复制持续存在于淋巴结等避难场所,则应高度重视改进针对这些部位的 ART 方案。为了调查当前 ART 方案中病毒持续复制的问题,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了 ART。八名儿童在不到十个月大的时候就开始接受抗逆转录病毒治疗,并在七到九年内显示出血浆病毒血症的抑制。两名儿童在病毒血症抑制之前分别患有不受控制的病毒血症十五个月和三十个月,并作为艾滋病毒复制和进化的阳性对照。后 2 名儿童显示出病毒进化的明确证据,而多种分析方法均未显示 ART 病毒血症抑制的 8 名儿童中任何一个有病毒进化的证据。最近报道的 ART 上 HIV-1 的进化速率为 6 × 10 –4个替换/位点/月,模拟的系统发育树与观察到的数据没有相似之处。总而言之,这些数据驳斥了这样的观点:持续的 HIV 复制在 ART 中很常见,并且是治愈 HIV-1 感染的主要障碍。
更新日期:2017-10-03
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