Centre de Recherche du Centre hospitalier de l'Université de Montréal and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Canada.
Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Clin Infect Dis. 2021 Aug 2;73(3):427-438. doi: 10.1093/cid/ciaa718.
Early antiretroviral therapy (ART) restricts the size of the human immunodeficiency virus (HIV) reservoir in infants. However, whether antiretroviral (ARV) prophylaxis given to exposed vertically infected children exerts similar effects remains unknown.
We measured total and integrated HIV DNA, as well as the frequency of CD4 T cells producing multiply spliced RNA (msRNA) after stimulation (inducible reservoir) in vertically infected Thai infants. Eighty-five infants were followed longitudinally for up to 3 years. We compared the size of the reservoir in children who received continuous ARV prophylaxis since birth vs those who never received or discontinued prophylaxis before initiating ART. We used samples from a cross-sectional cohort of 37 Thai children who had initiated ART within 6 months of life to validate our findings.
Before ART, levels of HIV DNA and the frequencies of cells producing msRNA were significantly lower in infants who received continuous ARV prophylaxis since birth compared to those in whom ARV prophylaxis was discontinued or never initiated (P < .020 and P < .001, respectively). Upon ART initiation, total and integrated HIV DNA levels decayed significantly in both groups (P < .01 in all cases). Interestingly, the initial differences in the frequencies of infected cells persisted during 3 years on ART. The beneficial effect of prophylaxis on the size of the HIV reservoir was confirmed in the cross-sectional study. Importantly, no differences were observed between children who discontinued prophylactic ARVs before starting ART and those who delayed ART initiation without receiving prior prophylaxis.
Neonatal ARV prophylaxis with direct transition to ART durably limits the size of the HIV reservoir.
早期抗逆转录病毒疗法（ART）可限制婴儿体内人类免疫缺陷病毒（HIV）储存库的大小。然而，暴露于垂直感染的儿童接受抗逆转录病毒（ARV）预防是否具有类似的效果尚不清楚。
我们测量了垂直感染的泰国婴儿的总 HIV DNA 和整合 HIV DNA，以及经刺激后（诱导性储存库）产生多聚体 RNA（msRNA）的 CD4 T 细胞的频率。85 名婴儿接受了长达 3 年的纵向随访。我们比较了从出生起即持续接受 ARV 预防的儿童与从未接受预防或在开始 ART 之前已停止预防的儿童的储存库大小。我们使用了在生命的头 6 个月内开始 ART 的 37 名泰国儿童的横断面队列样本来验证我们的发现。
在开始 ART 之前，与从未接受预防或已停止预防的儿童相比，从出生起即持续接受 ARV 预防的婴儿的 HIV DNA 水平和产生 msRNA 的细胞频率明显较低（分别为 P <.020 和 P <.001）。在开始 ART 后，两组的总 HIV DNA 和整合 HIV DNA 水平均显著下降（所有情况下 P <.01）。有趣的是，在开始 ART 后 3 年内，受感染细胞的初始差异仍持续存在。横断面研究证实了预防对 HIV 储存库大小的有益影响。重要的是，在开始 ART 之前停止预防性 ARV 与延迟开始 ART 而不接受先前预防的儿童之间未观察到差异。
直接过渡到 ART 的新生儿 ARV 预防可持久地限制 HIV 储存库的大小。
