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HIV brain latency as measured by CSF BcL11b relates to disrupted brain cellular energy in virally suppressed HIV infection

Cysique, Lucette A.a,b,c; Jugé, Laurianea,b; Lennon, Matthew J.c; Gates, Thomas M.c,d; Jones, Simon P.c; Lovelace, Michael D.b,c; Rae, Caroline D.a,b; Johnson, Tory P.e; Nath, Avindraf; Brew, Bruce J.b,c,d

doi: 10.1097/QAD.0000000000002076

Objective: We investigated whether HIV brain latency was associated with brain injury in virally suppressed HIV infection.

Design: Observational cross-sectional and longitudinal study.

Methods: The study included 26 virally suppressed HIV-infected men (61.5% with HIV-associated neurocognitive disorder) who undertook cerebrospinal fluid (CSF) analyses at baseline. They also completed a proton magnetic resonance spectroscopy (1H MRS) and neuropsychological assessments at baseline and 18 months. To quantify whether there was residual brain HIV transcription, we measured CSF HIV-tat. As an HIV brain latency biomarker, we used concentrations of CSF BcL11b – a microglia transcription factor that inhibits HIV transcription. Concurrently, we assessed neuroinflammation with CSF neopterin, neuronal injury with CSF neurofilament light-chain (NFL), and in-vivo neurochemistry with 1H MRS of N-acetyl aspartate (NAA), choline (Cho), creatine, myo-inositol (MI), glutamine/glutamate (Glx) in the frontal white matter (FWM), posterior cingulate cortex (PCC), and caudate nucleus area.

Results: Baseline adjusted regression models for neopterin, NFL, and tat showed that a higher CSF BcL11b was consistently associated with lower FWM creatine (when adjusted for neopterin: β = −0.30, P = 0.15; when adjusted for NFL: β = −0.47, P = 0.04; and when adjusted for tat: β = −0.47, P = 0.02). In longitudinal analyses, we found no time effect, but a consistent BcL11b altering effect on FWM creatine. The effect reached a significant moderate effect size range when corrected for CSF NFL (β = −0.36, P = 0.02) and CSF tat (β = −0.34, P = 0.02).

Conclusions: Reduced frontal white matter total creatine may indicate subclinical HIV brain latency-related injury. 1H MRS may offer a noninvasive option to measure HIV brain latency.

aNeuroscience Research Australia, Randwick

bSchool of Medical Sciences, UNSW Medicine, UNSW Sydney, Sydney

cPeter Duncan Neuroscience Research Unit, St. Vincent's Centre for Applied Medical Research

dDepartments of Neurology and Immunology, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia

eDepartment of Neurology, Johns Hopkins University, Baltimore

fSection of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.

Correspondence to Lucette A. Cysique, PhD, Neuroscience Research Australia, 139 Barker Street, Randwick, 2130 NSW, Australia. Tel: +61 2 93991880; e-mail:

Received 31 August, 2018

Accepted 5 October, 2018

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