Abstract
Initiation of combination antiretroviral therapy (cART) reduces inflammation in HIV-infected (HIV+) individuals. Recent studies demonstrated that diffusion MRI based extracellular free water (FW) modeling can be sensitive to neuroinflammation. Here, we investigate the FW in HIV-infection, its temporal evolution, and its association with blood markers, and cognitive scores. Using 96 age-matched participants, we found that FW was significantly elevated in grey and white matter in cART-naïve HIV+ compared to HIV-uninfected (HIV−) individuals at baseline. These increased FW values positively correlated with neurofilament light chain (NfL) and negatively correlated with CD4 counts. FW in grey and white matter, as well as NfL decreased in the HIV+ after 12 weeks of cART treatment. No significant FW differences were noted between the HIV+ and HIV− cohorts at 1 and 2-year follow-up. Results suggest that FW elevation in cART-naïve HIV+ participants is likely due to neuroinflammation. The correlation between FW and NfL, and the improvement in both FW and NfL after 12 weeks of cART treatment further reinforces this conclusion. The longer follow-up at 1 and 2 years suggests that cART helped control neuroinflammation as inferred by FW. Therefore, FW could be used as a biomarker to monitor HIV-associated neuroinflammation.
Highlights
Abbreviations FW Free water FWI Free water imaging neurofilament light chain (NfL) Neurofilament light chain combination antiretroviral therapy (cART) Combination antiretroviral therapy DTI Diffusion tensor imaging GM Grey matter WM White matter ROI Region of interest translocator protein (TSPO) Translocator protein Positron Emission Tomography (PET) Positron emission tomography extracellular space (ECS) Extracellular space viral load (VL) Viral load SE Standard error HAND HIV-associated neurocognitive disorders magnetization prepared rapid https://doi.org/10.1038/s41598-021-87801-y acquisition gradient-echo (MPRAGE) Magnetization prepared rapid acquisition gradient-echo Diffusion weighted images (DWI) Diffusion weighted imaging RSRB Research Subjects Review Board TR Repetition time TE Echo time field of view (FOV) Field of view
The relevance of FW as a marker of inflammation has been established by correlating FW with levels of microglial activation measured by TSPO via a PET study[23]
Four main findings emerged from this work: (1) FW index and NfL were higher in cART naïve HIV+ compared to the HIV− participants at baseline; (2) FW index and NfL decreased dramatically in GM and WM after 12 weeks of cART treatment in the HIV+ ; (3) FW levels were comparable between the HIV+ and HIV− at 1 year and 2 years of follow-up and similar trends were observed in NfL; and (4) baseline measures of FW index in GM and WM in the HIV+ subjects were associated with CD4 counts and NfL concentration
Summary
Abbreviations FW Free water FWI Free water imaging NfL Neurofilament light chain cART Combination antiretroviral therapy DTI Diffusion tensor imaging GM Grey matter WM White matter ROI Region of interest TSPO Translocator protein PET Positron emission tomography ECS Extracellular space VL Viral load SE Standard error HAND HIV-associated neurocognitive disorders MPRAGE Magnetization prepared rapid acquisition gradient-echo DWI Diffusion weighted imaging RSRB Research Subjects Review Board TR Repetition time TE Echo time FOV Field of view. Despite the successful suppression of viral replication and improved immune function with combination antiretroviral therapy (cART), approximately 30–50% of HIV-infected individuals (HIV+) still develop HIV-associated neurological disorders, including cognitive impairment[1]. Neuroinflammation due to HIV infection has been assessed using several neuroimaging biomarkers, including elevated glial markers via magnetic resonance spectroscopy (MRS)[7,8], increased glucose metabolism via Positron Emission Tomography (PET) and increased microglial activation via translocator protein (TSPO) PET tracers[9,10,11]. Di Biase et al.[26] recently reported increased FW in the frontal WM in adult rats prenatally exposed to maternal immune activation (i.e., exposed to polyriboinosinic-polyribocytidylic acid, Poly-I:C) Another recent work demonstrated elevated FW in WM in mice treated with interferon-gamma (Inf- γ) compared to controls[25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
