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

Abstract

Ran Tao,1 Xiaorong Peng,1 Xiang Liu,1 Junwei Su,1 Guanjing Lang,1 Ying Huang,1 Yafei Zhang,2 Biao Zhu1 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; 2PET Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Biao Zhu, Tel [phone], Fax [phone], Email [email protected]: Cryptococcal meningitis (CM) is a common opportunistic infection in patients with acquired immune deficiency syndrome. Although there is a standardized treatment for CM, some patients still have CM-associated immune reconstitution inflammatory syndrome (IRIS) after anti-cryptococcal and antiretroviral therapy, which manifests as cognitive impairment. We report two cases of CM-associated IRIS in human immunodeficiency virus (HIV) patients that were treated with lenalidomide. The treatment yielded a rapid clinical remission and improved cognitive function in both patients; their Montreal Cognitive Assessment (MoCA) and International HIV Dementia Scale (IHDS) scores improved. Furthermore, we evaluated changes in 32 cytokines in the cerebrospinal fluid of two patients and found that both MoCA and IHDS were significantly negatively correlated with inflammation-related factors (growth-related oncogene, interleukin [IL]-10, IL-2, IL-8, macrophage inflammatory protein-1β, tumor necrosis factor [TNF]-α) and significantly positively correlated with dementia-related factors (αβ 42 and total tau). Our study reveals the potential of lenalidomide in treating cognitive impairment caused by immune-mediated inflammation in patients with HIV-CM. Moreover, we speculate that lenalidomide improves cognitive function by regulating intracranial inflammation via multiple pathways, not only by TNF-α blocking.Keywords: acquired immune deficiency syndrome, Cryptococcus, immunomodulator, cognition, immune reconstitution inflammatory syndrome

Keywords

• acquired immune deficiency syndrome
• cryptococcus
• immunomodulator
• cognition
• immune reconstitution inflammatory syndrome