Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg.
Region Västra Götaland, Sahlgrenska University Hospital, Department of Infectious Diseases, Gothenburg, Sweden.
AIDS. 2021 Nov 1;35(13):2129-2136. doi: 10.1097/QAD.0000000000002980.
Persistent immune activation in the central nervous system and systemically are common in people living with HIV (PLHIV) despite antiretroviral therapy. It is not known whether this is generated by HIV replication or by other components such as coinfections and lifestyle-related factors.
The aim of this study was to determine the importance of different factors; it is crucial to find well matched HIV-negative controls. In this context, HIV-negative persons on preexposure prophylaxis (PrEP) may constitute a suitable control group to PLHIV with similar lifestyle-related factors.
Cerebrospinal fluid (CSF) and blood were collected from 40 HIV-negative persons on PrEP and 20 controls without PrEP. Biomarkers of immune activation, blood--brain barrier (BBB) integrity and neuronal injury were analysed.
CSF and serum β2-microglobulin, serum neopterin and CSF neurofilament light protein were higher in persons on PrEP compared with controls. Furthermore, persons on PrEP had higher CSF/plasma albumin ratio, and matrix metalloproteinase-3 concentrations, indicating BBB dysfunction. Of persons on PrEP, 90% were cytomegalovirus (CMV)-positive compared to 65% of the controls. CMV-positive individuals as a group had higher levels of serum β2-microglobulin than CMV-negative individuals (P < 0.05). Drug users had higher serum β2-microglobulin compared to nonusers (P < 0.01).
HIV-negative persons on PrEP had higher levels of biomarkers for immune activation, BBB impairment and neuronal injury, compared with volunteers without PrEP. Moreover, serum β2-microglobulin was higher in CMV-positive than in CMV-negative individuals and in drug users compared with nonusers. These findings are important to consider when analysing immune activation and CNS injury in PLHIV, and emphasize the importance of appropriate controls.
尽管接受了抗逆转录病毒疗法，HIV 感染者（PLHIV）的中枢神经系统和全身仍持续存在免疫激活。目前尚不清楚这是由 HIV 复制还是由其他因素（如合并感染和与生活方式相关的因素）引起的。
本研究旨在确定不同因素的重要性；找到匹配良好的 HIV 阴性对照至关重要。在这种情况下，接受暴露前预防（PrEP）的 HIV 阴性者可能构成与 PLHIV 具有相似生活方式相关因素的合适对照组。
从 40 名接受 PrEP 的 HIV 阴性者和 20 名未接受 PrEP 的对照者中采集脑脊液（CSF）和血液。分析免疫激活、血脑屏障（BBB）完整性和神经元损伤的生物标志物。
与对照组相比，接受 PrEP 的个体的 CSF 和血清β2-微球蛋白、血清新蝶呤和 CSF 神经丝轻蛋白水平更高。此外，接受 PrEP 的个体的 CSF/血浆白蛋白比值和基质金属蛋白酶-3 浓度更高，表明 BBB 功能障碍。与对照组的 65%相比，接受 PrEP 的个体中有 90%为巨细胞病毒（CMV）阳性。CMV 阳性个体的血清β2-微球蛋白水平高于 CMV 阴性个体（P<0.05）。与非使用者相比，药物使用者的血清β2-微球蛋白水平更高（P<0.01）。
与未接受 PrEP 的志愿者相比，接受 PrEP 的 HIV 阴性者的免疫激活、BBB 损伤和神经元损伤的生物标志物水平更高。此外，CMV 阳性个体的血清β2-微球蛋白水平高于 CMV 阴性个体，药物使用者的血清β2-微球蛋白水平高于非使用者。在分析 PLHIV 的免疫激活和中枢神经系统损伤时，这些发现很重要，并强调了使用适当对照的重要性。
