HIV Cure Research Center, Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University and Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
Department of General Internal Medicine and Infectious Diseases, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.
J Antimicrob Chemother. 2020 May 1;75(5):1311-1320. doi: 10.1093/jac/dkaa003.
Validated biomarkers to evaluate HIV-1 cure strategies are currently lacking, therefore requiring analytical treatment interruption (ATI) in study participants. Little is known about the safety of ATI and its long-term impact on patient health.
ATI safety was assessed and potential biomarkers predicting viral rebound were evaluated.
PBMCs, plasma and CSF were collected from 11 HIV-1-positive individuals at four different timepoints during ATI (NCT02641756). Total and integrated HIV-1 DNA, cell-associated (CA) HIV-1 RNA transcripts and restriction factor (RF) expression were measured by PCR-based assays. Markers of neuroinflammation and neuronal injury [neurofilament light chain (NFL) and YKL-40 protein] were measured in CSF. Additionally, neopterin, tryptophan and kynurenine were measured, both in plasma and CSF, as markers of immune activation.
Total HIV-1 DNA, integrated HIV-1 DNA and CA viral RNA transcripts did not differ pre- and post-ATI. Similarly, no significant NFL or YKL-40 increases in CSF were observed between baseline and viral rebound. Furthermore, markers of immune activation did not increase during ATI. Interestingly, the RFs SLFN11 and APOBEC3G increased after ATI before viral rebound. Similarly, Tat-Rev transcripts were increased preceding viral rebound after interruption.
ATI did not increase viral reservoir size and it did not reveal signs of increased neuronal injury or inflammation, suggesting that these well-monitored ATIs are safe. Elevation of Tat-Rev transcription and induced expression of the RFs SLFN11 and APOBEC3G after ATI, prior to viral rebound, indicates that these factors could be used as potential biomarkers predicting viral rebound.
目前缺乏评估 HIV-1 治愈策略的有效生物标志物，因此需要在研究参与者中进行分析性治疗中断（ATI）。目前对于 ATI 的安全性及其对患者健康的长期影响知之甚少。
评估 ATI 的安全性并评估预测病毒反弹的潜在生物标志物。
在 ATI 期间（NCT02641756），从 11 名 HIV-1 阳性个体的 4 个不同时间点收集 PBMCs、血浆和 CSF。通过基于 PCR 的测定法测量总和整合 HIV-1 DNA、细胞相关（CA）HIV-1 RNA 转录本和限制因子（RF）表达。通过测量 CSF 中的神经炎症和神经元损伤标志物[神经丝轻链（NFL）和 YKL-40 蛋白]来评估神经炎症和神经元损伤。此外，还测量了血浆和 CSF 中的神经氨酸、色氨酸和犬尿氨酸，作为免疫激活的标志物。
ATI 前后总 HIV-1 DNA、整合 HIV-1 DNA 和 CA 病毒 RNA 转录本无差异。同样，在病毒反弹前后，CSF 中 NFL 或 YKL-40 无明显增加。此外，ATI 期间免疫激活标志物没有增加。有趣的是，RFs SLFN11 和 APOBEC3G 在 ATI 后病毒反弹前增加。同样，在中断后病毒反弹前，Tat-Rev 转录本增加。
ATI 不会增加病毒储存库的大小，也不会显示出神经元损伤或炎症增加的迹象，表明这些经过良好监测的 ATI 是安全的。ATI 后病毒反弹前 Tat-Rev 转录和 RFs SLFN11 和 APOBEC3G 的诱导表达表明，这些因素可用作预测病毒反弹的潜在生物标志物。
