Initiation of antiretroviral therapy before detection of colonic infiltration by HIV reduces viral reservoirs, inflammation and immune activation
Initiation of antiretroviral therapy before detection of colonic infiltration by HIV reduces viral reservoirs, inflammation and immune activation
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DOI：
10.7448/ias.19.1.21163
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发表时间：
2016-09-15
影响因子：
6
通讯作者：
Ananworanich, Jintanat
中科院分区：
文献类型：
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作者：
Crowell, Trevor A.;Fletcher, James L. K.;Ananworanich, Jintanat
简介：HIV在感染后很快发生结肠浸润，建立一个持久的病毒库和治疗障碍。我们研究了急性HIV感染（AHI）期间可检测的结肠HIV RNA的病毒学和免疫学相关性及其对抗逆转录病毒治疗（ART）的反应。方法：从49,458份HIV筛查样本中，74名参与者在AHI期间入组，41名参与者同意选择乙状结肠镜检查，HIV RNA在均质结肠活检标本中被分类为可检测（>= 50拷贝/mg）或不可检测。比较各组和抗逆转录病毒治疗24周后血液、结肠和脑脊液中的生物标志物和艾滋病毒负担。结果：31名参与者（76%）可检测到结肠HIV RNA，并且与HIV暴露后持续时间较长（中位数为16天vs 11天，p = 0.02）、较高的中位数血浆细胞因子和炎症标志物水平(CXCL10 476 vs 148 pg/mL, p = 0.02; TNF-RII 1036 vs 649 pg/mL, p < 0.01；neopterin 2405 vs. 1368 pg/mL, p = 0.01)，血液（人白细胞抗原-抗原D相关(HLA-DR)/CD38表达14.4% vs. 7.6%, p < 0.01）和结肠（8.9% vs. 4.5%, p = 0.01）中CD8 + T细胞活化水平升高。抗逆转录病毒治疗24周后，基线可检测到结肠HIV RNA的参与者显示结肠粘膜单核细胞（CMMCs）中的总HIV DNA持续升高（中位数61比0拷贝/10(6)个CMMCs， p = 0.03），外周血单核细胞（PBMC）中的总HIV DNA有升高的趋势（41比1.5拷贝/10(6)个PBMCs， p = 0.06）。在免疫激活和炎症方面没有持久的差异。结论：在AHI期间开始抗逆转录病毒治疗时存在可检测的结肠HIV RNA与治疗24周后较高水平的前病毒DNA相关。在肠道中播种HIV可能对持久性病毒储存库的大小具有持久的影响，并且可能代表根除策略中的重要治疗靶点。
Introduction: Colonic infiltration by HIV occurs soon after infection, establishing a persistent viral reservoir and a barrier to cure. We investigated virologic and immunologic correlates of detectable colonic HIV RNA during acute HIV infection (AHI) and their response to antiretroviral treatment (ART).Methods: From 49,458 samples screened for HIV, 74 participants were enrolled during AHI and 41 consented to optional sigmoidoscopy, HIV RNA was categorized as detectable (>= 50 copies/mg) or undetectable in homogenized colon biopsy specimens. Biomarkers and HIV burden in blood, colon and cerebrospinal fluid were compared between groups and after 24 weeks of ART.Results: Colonic HIV RNA was detectable in 31 participants (76%) and was associated with longer duration since HIV exposure (median 16 vs. 11 days, p = 0.02), higher median plasma levels of cytokines and inflammatory markers (CXCL10 476 vs. 148 pg/mL, p = 0.02; TNF-RII 1036 vs. 649 pg/mL, p < 0.01; neopterin 2405 vs. 1368 pg/mL, p = 0.01) and higher levels of CD8 + T cell activation in the blood (human leukocyte antigen - antigen D related (HLA-DR)/CD38 expression 14.4% vs. 7.6%, p < 0.01) and colon (8.9% vs. 4.5%, p = 0.01). After 24 weeks of ART, participants with baseline detectable colonic HIV RNA demonstrated persistent elevations in total HIV DNA in colonic mucosal mononuclear cells (CMMCs) (median 61 vs. 0 copies/10(6) CMMCs, p = 0.03) and a trend towards higher total HIV DNA in peripheral blood mononuclear cells (PBMC) (41 vs. 1.5 copies/10(6) PBMCs, p = 0.06). There were no persistent differences in immune activation and inflammation.Conclusions: The presence of detectable colonic HIV RNA at the time of ART initiation during AHI is associated with higher levels of proviral DNA after 24 weeks of treatment. Seeding of HIV in the gut may have long-lasting effects on the size of persistent viral reservoirs and may represent an important therapeutic target in eradication strategies.