Outcome of Lenalidomide Treatment for Cognitive Impairment Caused by Immune Reconstitution Inflammatory Syndrome in Patients with HIV-Related Cryptococcal Meningitis

Purpose: Cognitive impairment associated with human immunodeficiency virus (HIV)-related cryptococcal meningitis (HCM) in the context of immune reconstitution inflammatory syndrome is difficult to address. This study was a follow-up of lenalidomide treatment outcomes in patients with HCM and cognitive impairment after complete cryptococcal clearance. Patients and Methods: Seven HCM patients with neuroinflammation and cognitive impairment after complete cryptococcal clearance were enrolled in this prospective study. Neurocognitive assessment, clinical examination and cerebrospinal fluid (CSF) assays were performed before and after lenalidomide treatment. Results: After lenalidomide treatment, the Montreal Cognitive Assessment [week (W) 0 (median [interquartile range]: 23.0 (13.0– 24.0) vs W24: 26.0 (24.0– 28.00), P=0.018] and International HIV Dementia Scale scores [W0: 9.0 (2.5– 10.5) vs W24: 11.0 (10.00– 12.0), P=0.028] improved significantly, mainly in the domain of memory function. There was no significant difference in the Center for Epidemiological Research Depression scores for anxiety and depression before and after treatment. Further stratified analyses revealed that the patients with cognitive improvement group had higher levels of CSF white blood cells [94.0 (44.0– 180.0) vs 0 (0– 1.5), P=0.032], CSF protein [4.9 (3.0– 6.6) vs 0.6 (0.5– 0.7), P=0.034], CSF albumin [318.5 (190.9– 346.5) vs 33.5 (30.4– 46.2), P=0.034], and CSF IgG [160.5 (73.8– 256. 0) vs 4.7 (4.3– 7.4), P=0.034] but a lower CSF glucose level [2.4 (2.0– 2.7) vs 2.8 (2.8– 3.9), P=0.032] than the patients with cognitive non-improvement group before treatment. CSF inflammatory cytokines of the growth-related oncogene, interleukin [IL]-10, granulocyte-colony stimulating factor, IL-6, IL-8, complement factor H, tumor necrosis factor-α, and α-2 macroglobulin were obviously decreased in patients with cognitive improvement group after lenalidomide treatment. Conclusion: Lenalidomide potentially reduces cognitive impairment caused by immune reconstitution inflammatory syndrome in patients with HCM after cryptococcal clearance by inhibiting intracranial inflammation. Keywords: lenalidomide, HIV, meningitis, cognitive impairment, Cryptococcus