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 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

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HIV Infections
Cerebrospinal Fluid
HIV
Brain
Intermediate Filaments
Creatine
Neopterin
Light
Neurochemistry
Caudate Nucleus
Gyrus Cinguli
Wounds and Injuries
Microglia
Inositol
Choline
Glutamine
Brain Injuries
Longitudinal Studies
Glutamic Acid
Transcription Factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Cysique, L. A., Jugé, L., Lennon, M. J., Gates, T. M., Jones, S. P., Lovelace, M. D., ... 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

HIV brain latency as measured by CSF BcL11b relates to disrupted brain cellular energy in virally suppressed HIV infection. / Cysique, Lucette A.; Jugé, Lauriane; Lennon, Matthew J.; Gates, Thomas M.; Jones, Simon P.; Lovelace, Michael D.; Rae, Caroline D.; Johnson, Tory; Nath, Avindra; Brew, Bruce J.

In: AIDS (London, England), Vol. 33, No. 3, 01.03.2019, p. 433-441.

Research output: Contribution to journalArticle

Cysique, LA, Jugé, L, Lennon, MJ, Gates, TM, Jones, SP, Lovelace, MD, Rae, CD, Johnson, T, Nath, A & Brew, BJ 2019, 'HIV brain latency as measured by CSF BcL11b relates to disrupted brain cellular energy in virally suppressed HIV infection', AIDS (London, England), vol. 33, no. 3, pp. 433-441. https://doi.org/10.1097/QAD.0000000000002076
Cysique, Lucette A. ; Jugé, Lauriane ; Lennon, Matthew J. ; Gates, Thomas M. ; Jones, Simon P. ; Lovelace, Michael D. ; Rae, Caroline D. ; Johnson, Tory ; Nath, Avindra ; Brew, Bruce J. / HIV brain latency as measured by CSF BcL11b relates to disrupted brain cellular energy in virally suppressed HIV infection. In: AIDS (London, England). 2019 ; Vol. 33, No. 3. pp. 433-441.
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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.",
author = "Cysique, {Lucette A.} and Lauriane Jug{\'e} and Lennon, {Matthew J.} and Gates, {Thomas M.} and Jones, {Simon P.} and Lovelace, {Michael D.} and Rae, {Caroline D.} and Tory Johnson and Avindra Nath and Brew, {Bruce J.}",
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T1 - HIV brain latency as measured by CSF BcL11b relates to disrupted brain cellular energy in virally suppressed HIV infection

AU - Cysique, Lucette A.

AU - Jugé, Lauriane

AU - Lennon, Matthew J.

AU - Gates, Thomas M.

AU - Jones, Simon P.

AU - Lovelace, Michael D.

AU - Rae, Caroline D.

AU - Johnson, Tory

AU - Nath, Avindra

AU - Brew, Bruce J.

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N2 - 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.

AB - 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.

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