Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection
Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection
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DOI：
10.1371/journal.pone.0033948
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发表时间：
2012-03-30
期刊：
影响因子：
3.7
通讯作者：
Kim, Jerome H.
中科院分区：
文献类型：
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作者：
Ananworanich, Jintanat;Schuetz, Alexandra;Kim, Jerome H.
背景：对早期艾滋病毒事件的了解有限，无法为预防和治疗策略提供信息。本研究旨在描述感染后最早的免疫学和病毒学 HIV 事件的特征，并研究新型治疗策略的使用。方法和结果：我们前瞻性地筛查了曼谷的 24,430 名受试者，并确定了 40 名 AHI 个体。 30 名泰国人入组（8 名 Fiebig I、5 名 Fiebig II、15 名 Fiebig III、2 名 Fiebig IV），其中 15 名完成了 24 周的 megaHAART（替诺福韦/恩曲他滨/依非韦伦/拉替拉韦/马拉维罗）。基线时乙状结肠活检完成率为 24/30，第 24 周时完成率为 13/15。基线时，中位年龄为 29 岁，83% 为 MSM。大多数有症状（87%），并感染了 R5 向性（77%）CRF01_AE（70%）。 CD4 中位数为 406 个细胞/mm(3)。 HIV RNA 为 5.5 log(10) 拷贝/ml。 Fiebig III（550 拷贝/10(6) PBMC）中的中位血液 HIV DNA 高于 Fiebig I（8 拷贝/10(6) PBMC）（p = 0.01），而 Fiebig III 中的 %CD4+CCR5+ 肠道 T 细胞中位数（19%）低于 Fiebig I（59%）（p = 0.0008）。 megaHAART 24 周后，血液中 14/15 和肠道中 13/13 的 HIV RNA 水平达到 50 个拷贝。第 0 周的血液 HIV DNA 总量预测第 24 周的病毒库大小 (p0.050)；基线时低于 40% 的受试者的 CD4+CCR5+ T 细胞从基线到第 24 周显着增加（14% vs. 71%，p = 0.02）。结论：肠道 T 细胞耗竭和 HIV 储存库播种随着 AHI 的进展而增加。 MegaHAART 与免疫恢复和减少储库大小相关。我们的研究结果可以为实现艾滋病毒无药缓解策略的研究提供信息。
Background: Limited knowledge exists on early HIV events that may inform preventive and therapeutic strategies. This study aims to characterize the earliest immunologic and virologic HIV events following infection and investigates the usage of a novel therapeutic strategy.Methods and Findings: We prospectively screened 24,430 subjects in Bangkok and identified 40 AHI individuals. Thirty Thais were enrolled (8 Fiebig I, 5 Fiebig II, 15 Fiebig III, 2 Fiebig IV) of whom 15 completed 24 weeks of megaHAART (tenofovir/emtricitabine/efavirenz/raltegravir/maraviroc). Sigmoid biopsies were completed in 24/30 at baseline and 13/15 at week 24. At baseline, the median age was 29 years and 83% were MSM. Most were symptomatic (87%), and were infected with R5-tropic (77%) CRF01_AE (70%). Median CD4 was 406 cells/mm(3). HIV RNA was 5.5 log(10) copies/ml. Median total blood HIV DNA was higher in Fiebig III (550 copy/10(6) PBMC) vs. Fiebig I (8 copy/10(6) PBMC) (p = 0.01) while the median %CD4+CCR5+ gut T cells was lower in Fiebig III (19%) vs. Fiebig I (59%) (p = 0.0008). After 24 weeks of megaHAART, HIV RNA levels of,50 copies were achieved in 14/15 in blood and 13/13 in gut. Total blood HIV DNA at week 0 predicted reservoir size at week 24 (p0.050); subjects with less than 40% at baseline had a significant increase in CD4+CCR5+ T cells from baseline to week 24 (14% vs. 71%, p = 0.02).Conclusions: Gut T cell depletion and HIV reservoir seeding increases with progression of AHI. MegaHAART was associated with immune restoration and reduced reservoir size. Our findings could inform research on strategies to achieve HIV drug-free remission.