MR spectroscopy in HIV associated neurocognitive disorder in the era of cART: a review

Neuroimaging has been a critical tool for understanding the neuropathological underpinnings observed in HIV. The pathophysiology of HAND is chiefly driven by neuroinflammation. Despite adhering to cART, low levels of viraemia probably persist in the brain in some patients leading to chronic immune activation with resultant neuroinflammation and consequent neuronal injury. MR spectroscopy has been widely used as a biomarker for the presence and severity of HAND in several studies. By studying the MRS signatures, it is possible to characterise the presence of neuroinflammation and neural injury. Furthermore, metabolite concentrations measured by MRS could be used as a quantitative indicator of HIV cerebral involvement, thereby affording the opportunity to assess the efficacy of cART in HAND. However, currently there are three significant limitations in the MRS HIV research literature: the relative paucity of prospective studies, the small number of regions of interrogation due to current methodology (single voxel MRS), and the evolving understanding of the impact of co-morbidities (e.g. ageing, mood disorders, alcoholism etc.) on MRS measurements. This review critically addresses the current literature of MRS studies in people living with HIV (PWH) with HAND to determine its value, especially in the context of the current cART era. In addition, we discuss technical considerations related to the disease and the future direction in HAND using MRS.