Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands; and.
Department of Pathology and Cell Biology, Columbia University, New York City, NY.
J Acquir Immune Defic Syndr. 2020 Apr 15;83(5):522-529. doi: 10.1097/QAI.0000000000002291.
Interventions aiming for an HIV cure would benefit from rapid elimination of virus after the onset of antiretroviral therapy (ART), by keeping the latent HIV reservoir small.
We investigated HIV suppression in 312 perinatally infected infants starting ART within 6 months after birth from the EPPICC (European Pregnancy and Paediatric HIV Cohort Collaboration).
To better understand kinetic differences in HIV suppression among infants, we investigated their individual viral load (VL) decay dynamics. We identified VL decay patterns and determined times to viral suppression (TTS). For infants with strictly declining VLs (n = 188), we used parameter fitting methods to estimate baseline VLs, decay rates, and TTS. We subsequently identified the parameters determining TTS by linear modeling.
The majority of infants suppress HIV VL after the onset of ART. Some children experienced a long TTS due to an "erratic" VL decay pattern. We cannot exclude that this is partly due to treatment complications and subsequent treatment changes, but these children were characterized by significantly lower CD4 percentages (CD4%) at start of treatment compared with those with a "clean" VL decline. Focusing on this "clean" subset, the TTS could be predicted by mathematical modeling, and we identified baseline VL and CD4% as the major factors determining the TTS.
As VL steeply increases and CD4% constantly decreases in untreated HIV-infected infants, the progression of an HIV infection is largely determined by these 2 factors. To prevent a further disease progression, treatment should be initiated early after contracting HIV, which consequently shortens TTS.
旨在实现 HIV 治愈的干预措施将受益于抗逆转录病毒治疗(ART)后病毒的快速清除,从而使潜伏的 HIV 储存量保持较小。
我们调查了 EPPICC(欧洲妊娠和儿科 HIV 队列合作组织)中 312 名在出生后 6 个月内开始接受 ART 的围产期感染婴儿的 HIV 抑制情况。
为了更好地了解婴儿中 HIV 抑制的动力学差异,我们研究了他们个体的病毒载量(VL)衰减动力学。我们确定了 VL 衰减模式并确定了病毒抑制时间(TTS)。对于具有严格下降 VL 的婴儿(n = 188),我们使用参数拟合方法来估计基线 VL、衰减率和 TTS。随后,我们通过线性建模确定了确定 TTS 的参数。
大多数婴儿在开始接受 ART 后抑制了 HIV VL。一些儿童由于 VL 衰减模式“不稳定”而经历了较长的 TTS。我们不能排除这部分是由于治疗并发症和随后的治疗改变,但这些儿童在开始治疗时的 CD4%(CD4%)明显低于 VL 下降“干净”的儿童。关注这个“干净”的亚组,TTS 可以通过数学建模来预测,我们确定基线 VL 和 CD4%是决定 TTS 的主要因素。
由于未治疗的 HIV 感染婴儿的 VL 急剧增加和 CD4%持续下降,HIV 感染的进展在很大程度上取决于这两个因素。为了防止疾病进一步进展,应在感染 HIV 后尽早开始治疗,从而缩短 TTS。