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Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART

Garvey, Lucy J.a,b; Pavese, Nicolac; Politis, Mariosc; Ramlackhansingh, Anilc; Brooks, David J.c; Taylor-Robinson, Simon D.a; Winston, Alana,b

doi: 10.1097/01.aids.0000432467.54003.f7
Clinical Science: Concise Communication

Background: Neuroinflammation plays an important role in HIV-associated neurological disorders; however, its role prior to the onset of symptomatic disease is unclear. We imaged microglial activation, the hallmark of neuroinflammation, in asymptomatic HIV-infected patients on effective combination ART.

Methods: Seven neurologically and cognitively asymptomatic adults with chronic HIV-infection and nine healthy volunteers were investigated with [11C]-PK11195 PET, a marker of translocator protein (TSPO) expressed by activated microglia. In the HIV-infected patients, cognitive speed, accuracy and executive function were also assessed. Between-group differences in [11C]-PK11195 binding potential were localized throughout the brain with statistical parametric mapping (SPM) and associations between levels of [11C]-PK11195 binding and cognitive performance were interrogated using linear regression modelling.

Results: In HIV-infected patients, Statistical parametric mapping detected clusters of significantly increased [11C]-PK11195 binding in corpus callosum (P = 0.001), anterior cingulate (P = 0.001), posterior cingulate (P = 0.008) and temporal (P = 0.026) and frontal (P = 0.038) areas. Cognitive functions were intact in the HIV group, however, a significant association between greater [11C]-PK11195 binding and poorer executive function performance was observed in the anterior cingulate (P = 0.031), corpus callosum and posterior cingulate (P = 0.001).

Conclusion: Despite effective control of HIV infection, neuroinflammation, as evidenced by the presence of focal cortical areas of activated microglia, occurs in asymptomatic HIV-infected patients and levels correlate with poorer executive performance. Further studies are needed to establish whether detection of activated microglia in HIV-infected patients represents a marker of future neurocognitive decline.

aDepartment of Medicine, Faculty of Medicine, Imperial College London, St Mary's Hospital Campus, Norfolk Place

bDepartment of HIV and GU Medicine, Imperial College Healthcare NHS Trust

cDivision of Brain Sciences, Imperial College London, Hammersmith Hospital Campus, London, UK.

Correspondence to Dr Nicola Pavese, Neurology Imaging Unit, 1st Floor, B Block, Imperial College London, Division of Brain Sciences, Hammersmith Campus, DuCane Road, London W12 0NN, UK. Tel: +44 020 3313 3766; fax: +44 020 3313 4320; e-mail: nicola.pavese@imperial.ac.uk

Received 23 May, 2013

Revised 20 June, 2013

Accepted 24 June, 2013

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© 2014 Lippincott Williams & Wilkins, Inc.