Mutli-modal MRI confirms HIV-1-linked neurometabolomic impairments in humanized mice

Motivation: While anti-retroviral therapy (ART) is essential for combating the type-one human immunodeficiency virus (HIV-1), patients with undetectable viral load still experience HIV-associated neurocognitive disorders. Goal(s): We aimed to use the chemical exchange saturation transfer (CEST) effects of brain metabolites with MRI to elucidate HIV-associated neurocognitive outcomes on ART patients. Approach: Humanized mice were infected with HIV-1, then given daily treatment of ART or vehicle. CEST-MRI and MRS were used to evaluate brain metabolites at four key timepoints. Results: Untreated mice showed declining 2ppm and 3ppm CEST signal in key brain regions, alongside increasing NOE signal. This was partially validated with MRS. Impact: The metabolic insights that CEST-MRI offers to HIV immunological care may aid in the development of increasingly effective ART drugs, such as long-acting injectables. Increased efficacy of ART will allow for increased quality of life for people living with HIV.