Abstract / Summary
Abstract Background Cytomegalovirus (CMV) neurologic disease is an uncommon but severe complication of advanced HIV infection. Evidence guiding management is limited, and the implications of programmed cell death protein 1 (PD-1) blockade when low-level cerebrospinal fluid (CSF) CMV DNA remains detectable are unknown. Case presentation A 57-year-old man with HIV-associated Epstein-Barr virus-encoded RNA-positive diffuse large B-cell lymphoma had CD4⁺ T-cell counts persistently below 100 cells/µL. He subsequently developed fever, dizziness, and somnolence. During the diagnostic evaluation, CSF CMV DNA was 1.53 × 10⁷ IU/mL, compared with 96,000 IU/mL in paired plasma. Major alternative Central Nervous System (CNS) opportunistic infections and CNS lymphoma were not identified, supporting a diagnosis of probable CNS CMV disease. Prolonged ganciclovir-based therapy with foscarnet coadministration reduced CSF CMV DNA to 150 IU/mL one day before the first sintilimab dose, which was administered for lymphoma consolidation. CSF CMV DNA was first documented as undetectable 27 days later and remained undetectable through October 2025. Serial monitoring showed recovery of the absolute peripheral CD8⁺ T-cell count from a pre-sintilimab nadir, early enrichment of the effector CD8⁺ T-cell compartment, later partial re-equilibration of effector-memory CD8⁺ T cells, subset-specific PD-1⁺ T-cell dynamics, and selective CSF cytokine activation without clinically apparent inflammatory worsening. Conclusions The overall virologic decline was primarily attributable to anti-CMV therapy. The temporal association among PD-1 blockade, transient T-cell immunophenotypic remodeling, and the first documented undetectable CSF CMV DNA result raises the hypothesis that sintilimab-associated immune modulation may have contributed to the final conversion of residual low-level CSF CMV DNA to undetectability. However, causality cannot be established because antiviral therapy and broader immune recovery were ongoing. This report provides limited tolerability information for PD-1 blockade under continued antiviral coverage and a low residual CSF CMV DNA burden.