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Lenalidomide Improves Cognitive Function and Reduces Immune Reconstitution Inflammatory Syndrome in HIV-1-Related

Ran Tao1, Xiaorong Peng1, Xiang Liu1

  • 1The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Journal of Inflammation Research
|May 19, 2022
PubMed

Insights

Lenalidomide shows promise in treating cognitive impairment in HIV patients with cryptococcal meningitis-associated immune reconstitution inflammatory syndrome (IRIS). This treatment rapidly improved cognitive function by reducing inflammation.

Area of Science:

  • Neuroimmunology
  • Infectious Diseases
  • Pharmacology

Background:

  • Cryptococcal meningitis (CM) is a significant opportunistic infection in individuals with acquired immune deficiency syndrome (AIDS).
  • Immune reconstitution inflammatory syndrome (IRIS) can develop post-treatment for CM and antiretroviral therapy, leading to cognitive impairment.
  • Standard treatments for CM do not always prevent CM-associated IRIS and subsequent cognitive decline.

Observation:

  • Two cases of human immunodeficiency virus (HIV) patients with CM-associated IRIS and cognitive impairment were treated with lenalidomide.
  • Lenalidomide administration resulted in rapid clinical remission and noticeable improvements in cognitive function for both patients.
  • Cognitive assessments, including the Montreal Cognitive Assessment (MoCA) and International HIV Dementia Scale (IHDS), showed significant improvement post-treatment.

Findings:

  • Cerebrospinal fluid cytokine analysis revealed negative correlations between cognitive scores (MoCA, IHDS) and inflammation markers (GRO, IL-10, IL-2, IL-8, MIP-1β, TNF-α).
  • Conversely, cognitive scores positively correlated with dementia markers (Aβ42, total tau).
  • Lenalidomide's efficacy suggests a role in modulating the inflammatory pathways contributing to cognitive dysfunction.

Implications:

  • Lenalidomide presents a potential therapeutic strategy for managing cognitive impairment in HIV patients experiencing CM-associated IRIS.
  • The drug may improve cognitive function by targeting and regulating intracranial inflammation through multifaceted pathways, beyond just TNF-α inhibition.
  • Further research into lenalidomide's neuroprotective mechanisms in HIV-associated neuroinflammation is warranted.
Keywords:
Cryptococcusacquired immune deficiency syndromecognitionimmune reconstitution inflammatory syndromeimmunomodulator

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