Seeing Is Believing: Nuclear Imaging of HIV Persistence

Abstract

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, in vivo 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.

Reinventing Molecular Imaging with Total-Body PET, Part II

“… 58 , 59 Similarly, total-body human immunodeficiency virus burden in vivo has been suggested using TB-PET imaging. 60 …”

Imaging modalities for cardiovascular phenotyping in asymptomatic people living with HIV

“…37 Several studies using 18 F-FDG PET/CT have been conducted to (i) provide evidence of arterial inflammation in PLWH, (ii) investigate the effects of HIV on CVD, and (iii) assess treatment effect in PLWH. 38,39 PLWH with undetectable viral load have significantly higher arterial inflammation in the aorta compared to non-infected controls, and similar aortic inflammation compared to atherosclerotic controls. 39 These findings supported an emerging role of macrophage arterial infiltration in subclinical atherosclerotic process among PLWH.…”

Insights Into Persistent HIV-1 Infection and Functional Cure: Novel Capabilities and Strategies

“…However, these imaging-based approaches remain limited by the scarce accessibility of tissue specimens from clinical trials as opposed to blood and by the two-dimensional analysis of a few representative sections, which is based on the assumption that observations made can be inferred to the entire organ. In this regard, it is encouraging to see the emergence of total body positron emission tomography (PET) scanning ( Santangelo et al, 2015 ; Henrich et al, 2019 ; Taylor et al, 2021 ) and whole organ imaging with novel tissue clearing technologies coupled with light-sheet microscopy ( Tomer et al, 2014 ), which may represent new frontiers to detect viral reservoirs and broaden our understanding of virus persistence in tissue. Other approaches to identifying replication-competent reservoirs measure translation competent proviruses ( Baxter et al, 2016 ).…”