Checking the Checkpoint Inhibitors: A Case of Autoimmune Diabetes After PD-1 Inhibition in a Patient with HIV

Immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) is a known immune-related adverse event (irAE) following treatment with programmed cell death protein 1 (PD-1), with a reported 0.9% incidence. We hereby present the first case, to our knowledge, of ICI-DM following ICI use in a human immunodeficiency virus (HIV) patient. In this case, a 48-year-old man with HIV stable on highly active antiretroviral therapy (HAART) was diagnosed with Hodgkin lymphoma and initiated treatment with the PD-1 inhibitor nivolumab. His lymphoma achieved complete response after 5 months. However, at month 8, he reported sudden polydipsia and polyuria. Labs revealed a glucose level of 764 mg/dL and glycated hemoglobin A1c (HbA1c) of 7.1%. Low C-peptide and elevated glutamic acid decarboxylase 65 (GAD65) antibody levels confirmed autoimmune DM, and he was started on insulin. Major histocompatibility complex class II genetic analysis revealed homozygous HLA DRB1*03-DQA1*0501-DQB1*02 (DR3-DQ2), which is a known primary driver of genetic susceptibility to type 1 DM. Autoimmune DM has been reported as an ICI-associated irAE. However, patients with immunocompromising conditions such as HIV are usually excluded from ICI trials. Therefore, little is known about such irAEs in this population. In this case, risk of ICI-DM as an irAE was likely increased by several factors including family history, a high-risk genetic profile, islet-related immunologic abnormalities, active lymphoma, and HIV infection with a possible immune reconstitution event. Clinicians should maintain a high index of suspicion for development of irAEs associated with ICI, particularly as use of these therapies broadens. Thorough investigation for presence of higher-risk features should be conducted and may warrant inclusion of pre-therapy genetic and/or autoantibody screening.