Division of Experimental Medicine, Department of Medicine, University of San Francisco, San Francisco, CA, United States.
Division of Cardiology, Department of Medicine, University of San Francisco, San Francisco, CA, United States.
Front Immunol. 2019 Sep 12;10:2077. doi: 10.3389/fimmu.2019.02077. eCollection 2019.
A major obstacle to HIV eradication is the presence of infected cells that persist despite suppressive antiretroviral therapy (ART). HIV largely resides outside of the peripheral circulation, and thus, numerous anatomical and lymphoid compartments that have the capacity to harbor HIV are inaccessible to routine sampling. As a result, there is a limited understanding of the tissue burden of HIV infection or anatomical distribution of HIV transcriptional and translational activity. Novel, non-invasive, methods are urgently needed to address this fundamental gap in knowledge. In this review, we discuss past and current nuclear imaging approaches that have been applied to HIV infection with an emphasis on current strategies to implement positron emission tomography (PET)-based imaging to directly visualize and characterize whole-body HIV burden. These imaging approaches have various limitations, such as the potential for limited PET sensitivity and specificity in the setting of ART suppression or low viral burden. However, recent advances in high-sensitivity, total-body PET imaging platforms and development of new radiotracer technologies that may enhance anatomical penetration of target-specific tracer molecules are discussed. Potential strategies to image non-viral markers of HIV tissue burden or focal immune perturbation are also addressed. Overall, emerging nuclear imaging techniques and platforms may play an important role in the development of novel therapeutic and HIV reservoir eradication strategies.
艾滋病病毒根除的一个主要障碍是存在受感染的细胞,尽管有抑制性抗逆转录病毒疗法(ART),这些细胞仍持续存在。HIV 主要存在于外周循环之外,因此,许多具有容纳 HIV 能力的解剖和淋巴组织部位无法进行常规采样。因此,人们对 HIV 感染的组织负担或 HIV 转录和翻译活性的解剖分布知之甚少。迫切需要新的、非侵入性的方法来解决这一知识的基本差距。在这篇综述中,我们讨论了过去和现在应用于 HIV 感染的核成像方法,重点是当前实施正电子发射断层扫描(PET)成像的策略,以直接可视化和描述全身 HIV 负担。这些成像方法存在各种局限性,例如在 ART 抑制或病毒载量低的情况下,PET 的灵敏度和特异性可能有限。然而,讨论了高灵敏度、全身 PET 成像平台的最新进展以及新的示踪剂技术的开发,这些技术可能增强针对特定靶标的示踪剂分子的解剖穿透性。还讨论了用于成像 HIV 组织负担或局部免疫扰动的非病毒标志物的潜在策略。总体而言,新兴的核成像技术和平台可能在开发新的治疗和 HIV 储库清除策略方面发挥重要作用。