Prospective antiretroviral treatment of asymptomatic, HIV-1 infected controllers.
Prospective antiretroviral treatment of asymptomatic, HIV-1 infected controllers.
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DOI：
10.1371/journal.ppat.1003691
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Deeks SG
中科院分区：
文献类型：
--
作者：
Hatano H;Yukl SA;Ferre AL;Graf EH;Somsouk M;Sinclair E;Abdel-Mohsen M;Liegler T;Harvill K;Hoh R;Palmer S;Bacchetti P;Hunt PW;Martin JN;McCune JM;Tracy RP;Busch MP;O'Doherty U;Shacklett BL;Wong JK;Deeks SG
对在缺乏抗逆转录病毒治疗 (ART) 的情况下能够维持低血浆 HIV RNA 水平的 HIV 感染“控制者”的研究可能为 HIV 治疗和疫苗策略提供见解。尽管血浆病毒血症水平保持在非常低的水平，但控制者却提高了免疫激活并加速了动脉粥样硬化。然而，低水平复制对这些现象的贡献程度尚不清楚。 16 名无症状控制者接受了为期 24 周的 ART 前瞻性治疗。通过 ART，控制者的超敏感血浆和直肠 HIV RNA 水平在统计上显着降低。 ART 治疗后，血液和肠粘膜中 T 细胞活化/功能障碍的标志物也大幅下降。在 ART 前血浆 HIV RNA 水平低于常规检测（<40 拷贝/mL）的“精英”控制者子集中也观察到类似的减少。这些数据证实，HIV 复制在控制者体内持续存在，并导致慢性炎症状态。应考虑对这些人进行 ART（ClinicalTrials.gov NCT01025427）。 HIV 感染“控制者”是极少数 HIV 血清呈阳性但在没有抗逆转录病毒治疗 (ART) 的情况下仍能维持低血浆 HIV RNA 水平的个体。人们对描述这些独特个体的特征产生了浓厚的兴趣，因为他们被认为是艾滋病毒“功能性治愈”的潜在模型。此前，我们的团队已经证明，控制者的 T 细胞激活水平升高并加速动脉粥样硬化，这表明极低水平的病毒复制可能导致不成比例的高水平免疫激活。然而，病毒复制对这些结果的贡献程度尚不清楚。因此，我们在一组无症状 HIV 感染控制者中进行了首次 ART 启动的前瞻性研究，以确定用 ART 治疗控制者的病毒学和免疫学效果。通过 ART，控制者的超敏感血浆 HIV RNA、直肠 HIV RNA 以及血液和肠粘膜中 T 细胞活化/功能障碍的标记物显着降低。在 ART 前血浆 HIV RNA 水平极低（<40 拷贝/mL）的“精英”控制者子集中也观察到类似的减少。这些数据表明，HIV 复制在控制者体内持续存在，并导致慢性炎症状态。
The study of HIV-infected “controllers” who are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy (ART) may provide insights for HIV cure and vaccine strategies. Despite maintaining very low levels of plasma viremia, controllers have elevated immune activation and accelerated atherosclerosis. However, the degree to which low-level replication contributes to these phenomena is not known. Sixteen asymptomatic controllers were prospectively treated with ART for 24 weeks. Controllers had a statistically significant decrease in ultrasensitive plasma and rectal HIV RNA levels with ART. Markers of T cell activation/dysfunction in blood and gut mucosa also decreased substantially with ART. Similar reductions were observed in the subset of “elite” controllers with pre-ART plasma HIV RNA levels below conventional assays (<40 copies/mL). These data confirm that HIV replication persists in controllers and contributes to a chronic inflammatory state. ART should be considered for these individuals (ClinicalTrials.gov NCT01025427). HIV-infected “controllers” are rare individuals who are HIV-seropositive but are able to maintain low levels of plasma HIV RNA in the absence of antiretroviral therapy (ART). There has been intense interest in characterizing these unique individuals because they have been considered as a potential model for a “functional cure” of HIV. Previously, our group has shown that controllers have elevated levels of T cell activation and accelerated atherosclerosis, suggesting that very low levels of viral replication may lead to disproportionately high levels of immune activation. However, the degree to which viral replication contributes to these outcomes is not known. We therefore conducted the first, prospective study of ART initiation in a cohort of asymptomatic HIV-infected controllers, in order to determine the virologic and immunologic effects of treating controllers with ART. Controllers had a significant decreases in ultrasensitive plasma HIV RNA, rectal HIV RNA, and markers of T cell activation/dysfunction in blood and gut mucosa with ART. Similar reductions were observed in the subset of “elite” controllers with extremely low pre-ART plasma HIV RNA levels (<40 copies/mL). These data suggest that HIV replication persists in controllers and contributes to a chronic inflammatory state.
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