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

Lucette A. Cysique, Lauriane Jugé, Matthew J. Lennon, Thomas M. Gates, Simon P. Jones, Michael D. Lovelace, Caroline D. Rae, Tory P. Johnson, Avindra Nath, Bruce J. Brew

Research output: Contribution to journalArticle

Abstract

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 (H 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 H 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. H MRS may offer a noninvasive option to measure HIV brain latency.

Original languageEnglish (US)
Pages (from-to)433-441
Number of pages9
JournalAIDS (London, England)
Volume33
Issue number3
DOIs
StatePublished - Mar 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Cysique, L. A., Jugé, L., Lennon, M. J., Gates, T. M., Jones, S. P., Lovelace, M. D., Rae, C. D., Johnson, T. P., Nath, A., & Brew, B. J. (2019). HIV brain latency as measured by CSF BcL11b relates to disrupted brain cellular energy in virally suppressed HIV infection. AIDS (London, England), 33(3), 433-441. https://doi.org/10.1097/QAD.0000000000002076