Exacerbation of CMV and Nontuberculous Mycobacterial Infections Following PD-1 Blockade for HIV-Associated Kaposi Sarcoma

Abstract

Blockade of the co-inhibitory receptor PD-1 enhances anti-tumor responses by boosting the function of antigen-specific T cells. Although rare, PD-1 blockade in patients with cancer can lead to exacerbation of infection-associated pathology. Here we detail the case of a 38-year-old man who was enrolled in a clinical trial for assessment of the safety and activity of anti-PD-1 therapy for Kaposi sarcoma in people with HIV (PWH) well-controlled on anti-retroviral therapy (ART). Less than a week after receiving the first dose of anti-PD1 antibody (pembrolizumab), he presented with severe abdominal pain associated with sudden exacerbations of pre-existing cytomegalovirus (CMV) enteritis and nontuberculous mycobacterial mesenteric lymphadenitis. Plasma biomarkers of gastrointestinal (GI) tract damage were highly elevated compared to healthy controls, consistent with HIV associated loss of gut epithelial barrier integrity. Moreover, CMV-specific CD8 T cells expressed high levels of PD-1, and seven days following PD-1 blockade there was an increase in the frequency of activated CD38 + Ki67+ CMV-specific CD8 T cells. This case highlights the potential for PD-1 blockade to drive rapid exacerbations of inflammatory symptoms when administered to individuals harboring multiple unresolved infections.