Suspected Immune-Related Adverse Events With an Anti-PD-1 Inhibitor in Otherwise Healthy People With HIV

To the Editors: Reversing T-cell exhaustion using antibodies to immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy. Because T-cell exhaustion, mediated by programmed death-1/programmed death ligand-1 (PD-1/PD-L1), may be a barrier to HIV cure and CD4+ T cells expressing PD-1 are enriched for latent HIV, treatment with anti-PD-1 antibodies may provide a strategy for targeting the latent HIV reservoir. Given that elimination of latently infected cells harboring replication-competent provirus will be necessary to cure HIV infection, we initiated a phase I/IIa, double-blind, placebo-controlled, dose-escalating safety and immunotherapeutic study of 2 infusions of an anti-PD-1 antibody (cemiplimab) in virally suppressed persons with HIV (PWH). Although participants were not anticipated to receive direct benefit from this study and ICIs are associated with potentially irreversible immune-related adverse events (irAEs), feedback from PWH and the scientific and HIV communities encouraged the team to pursue this HIV cure intervention. Moreover, preliminary data provided a reasonable expectation that cemiplimab would improve HIV-specific immune responses, reverse HIV latency, and, thus, advance the field. This risk versus benefit assessment led to the incorporation of strict measures to limit risk to participants (eg, history of autoimmune disease was exclusionary). Four of the 5 participants enrolled were randomized to receive 0.3 mg/kg of cemiplimab at weeks 0 and 6; one participant received placebo. Possible irAEs occurred in 2 participants