Cognitive Impairment in HIV Infection

Despite the success of combination antiretroviral therapy (ART) in transforming HIV into a manageable chronic condition, a substantial proportion of individuals experience neurocognitive deficits collectively known as HIV-associated neurocognitive disorders (HAND). These range from asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND) to HIV-associated dementia (HAD). Even in patients with suppressed plasma viraemia, residual viral transcription within central nervous system (CNS) reservoirs, sustained immune activation and microglial inflammation contribute to synaptic dysfunction and axonal injury. Cerebrospinal fluid (CSF) biomarkers such as neurofilament light chain and neopterin reveal ongoing neuronal damage and immune activation, respectively. Clinically, affected domains include attention, processing speed, executive function and motor coordination, with even subtle declines undermining daily functioning, adherence to therapy and quality of life. The persistence of HAND in the cART era underscores the need to address CNS viral persistence, optimise drug penetration across the blood–brain barrier and develop adjunctive neuroprotective strategies. Globally, neurocognitive impairment in HIV imposes a growing burden on healthcare systems and highlights the imperative for integrated neurological screening and intervention in routine HIV care.

Research from Nature Portfolio

Recent studies have shown that HIV-1 RNAs persist in extracellular vesicles (EVs) isolated from both CSF and serum of people on suppressive ART. Quantitative analysis of EV-associated transcripts reveals compartmentalisation of defective viral RNAs in the CNS, with higher EV RNA loads correlating with worse neurocognitive performance over time. These findings indicate that latent HIV transcription contributes to ongoing CNS complications and may be underestimated by conventional plasma monitoring alone.

Cognitive Impairment in HIV Infection publication trend

The graph below shows the total number of articles in cognitive impairment in hiv infection across all publications each year (not limited to Nature Index journals).

Technical terms

Antiretroviral therapy (ART): Combination of drugs that suppress HIV replication and reduce plasma viral load.

Extracellular vesicles (EVs): Membrane-bound particles secreted by cells that carry proteins, nucleic acids and lipids.

Cerebrospinal fluid (CSF): Clear fluid in the subarachnoid space used for biomarker assessment of CNS disorders.

Asymptomatic neurocognitive impairment (ANI): Subclinical cognitive deficits detected by formal testing without evident functional decline.

Blood–brain barrier (BBB): Endothelial interface that regulates exchange between the circulation and CNS.

Neurofilament light chain (NFL): Cytoskeletal protein fragment released into CSF upon axonal injury, serving as a sensitive biomarker.

Neuroinflammation: Activation of glial cells and release of inflammatory mediators within the CNS.

References

1. HIV-1 RNA in extracellular vesicles is associated with neurocognitive outcomes. Nature Communications (2024).
2. Ionic Liquid Coating‐Driven Nanoparticle Delivery to the Brain: Applications for NeuroHIV. Advanced Science (2024).
3. Neurosymptomatic HIV-1 CSF escape is associated with replication in CNS T cells and inflammation. Journal of Clinical Investigation (2024).
4. HIV-1-associated neurocognitive disorder: epidemiology, pathogenesis, diagnosis, and treatment. Journal of Neurology (2017).
5. Biomarker Evidence of Axonal Injury in Neuroasymptomatic HIV-1 Patients. PLOS ONE (2014).
6. Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection. AIDS Research and Therapy (2010).
7. The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence?. BMC Infectious Diseases (2011).
8. Rapid inflammasome activation in microglia contributes to brain disease in HIV/AIDS. Retrovirology (2014).