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The impact of cryptococcosis on cerebral structure and MRI characteristics in people living with HIV (PWH) who have cryptococcal meningoencephalitis remains underexplored. Existing evidence mainly comes from small-scale studies.This study aimed to clarify the effects of cryptococcal meningoencephalitis on brain structural changes and MRI features in PWH. A total of 190 patients with intracranial cryptococcosis were enrolled and categorized, based on HIV serostatus, into the PWH group (n = 127) and the people linving without HIV(PWOH) group (n = 63). Laboratory parameters, brain volumes, and MRI findings were compared between the two groups. In the two groups, continuous variables were compared using the independent samples t-test, while categorical data were analyzed using the χ² test. The PWH with cryptococcosis group was significantly younger than the PWOH group (51 ± 13 years vs. 60 ± 14 years, P < 0.05). Additionally, this group showed lower peripheral blood leukocyte, platelet, hemoglobin, and lymphocyte counts (all P < 0.05).Cerebrospinal fluid (CSF) analysis in PWH showed lower protein levels (0.97 ± 0.9 vs. 1.31 ± 1.11), decreased cell counts—predominantly polymorphonuclear cells—and increased glucose levels (2.18 ± 1.03 vs. 1.64 ± 1.29) compared with the PWOH. Brain volumetric analysis revealed that the PWH with cryptococcosis group had a reduction in total brain tissue volume (70.1 ± 3.9 vs. 72.0 ± 4.3), a decreased proportion of white matter (33.3 ± 2.9 vs. 35.3 ± 3.3), and an increased proportion of CSF space (29.9 ± 3.9 vs. 28.0 ± 4.3) (all P < 0.05). Additionally, the relative volume proportions of the hippocampus (0.68 ± 0.27 vs. 0.52 ± 0.25) and basal ganglia (1.71 ± 0.41 vs. 1.48 ± 0.34) were significantly larger in the PWH (P < 0.05). On MRI, leptomeningeal enhancement was more frequently observed in the PWOH group, whereas the PWH with cryptococcosis group demonstrated a higher incidence of lacunar infarcts. PWH with intracranial cryptococcosis show cerebral white matter atrophy, accompanied by compensatory expansion of cerebrospinal fluid (CSF) volume and a relative enlargement of deep gray matter nuclei, particularly affecting the hippocampus and basal ganglia. These structural changes are associated with inflammatory alterations in CSF and an elevated risk of vascular complications, such as lacunar infarction.