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Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART
Lucy J Garvey1, Nicola Pavese, Marios Politis
1aDepartment 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.
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.
Insights
Neuroinflammation is present in asymptomatic HIV patients, even with effective treatment. Increased microglial activation correlates with poorer executive function, suggesting a risk for future cognitive decline.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Neuroinflammation is implicated in HIV-associated neurological disorders.
- The role of neuroinflammation before symptomatic disease onset in HIV patients remains unclear.
- Microglial activation, a key marker of neuroinflammation, was studied in asymptomatic HIV patients on combination antiretroviral therapy (ART).
Purpose of the Study:
- To investigate microglial activation in neurologically asymptomatic HIV-infected individuals.
- To determine the relationship between neuroinflammation markers and cognitive function in this population.
Main Methods:
- Positron Emission Tomography (PET) with [11C]-PK11195, a marker for translocator protein (TSPO) on activated microglia, was used.
- Seven asymptomatic HIV-infected adults and nine healthy controls were scanned.
- Cognitive functions (speed, accuracy, executive function) were assessed in HIV patients, and statistical parametric mapping (SPM) analyzed brain-wide differences in [11C]-PK11195 binding.
Main Results:
- Increased [11C]-PK11195 binding, indicating microglial activation, was found in the corpus callosum, anterior cingulate, posterior cingulate, temporal, and frontal areas of HIV patients.
- Cognitive functions were generally intact in the HIV group.
- Higher [11C]-PK11195 binding in the anterior cingulate, corpus callosum, and posterior cingulate was significantly associated with poorer executive function.
Conclusions:
- Focal cortical areas of activated microglia are present in asymptomatic HIV patients despite effective HIV control.
- The level of microglial activation correlates with diminished executive performance.
- Further research is required to ascertain if activated microglia detection predicts future neurocognitive decline in HIV patients.
