Transient HIV Reservoirs and Interleukin-6 Increase After Anti-Programmed Death-1 Antibody Infusion in HIV Patients with Lung Cancer

Abstract

Background: The purpose of this study is to examine the dynamic effects of anti-programmed death (PD)-1 antibody treatment on HIV reservoirs and inflammatory cytokines in patients with HIV infections who were diagnosed with non-small cell lung cancer (NSCLC). Methods: This is a clinical trial in which three HIV patients with NSCLC were administered 14 infusions of anti-PD-1 antibody at 21-day intervals. Blood samples were collected from the participants before each infusion (0 h), and at 2 h, 24 h, and 7 days after each infusion of anti-PD-1 monoclonal antibody. The levels of cell-associated HIV RNA (CA-HIV-RNA), HIV DNA, and inflammatory cytokines (including interferon [IFN]-α, IFN-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-2, IL-4, IL-6, IL-10, and IL-17A) were assessed at each timepoint. Results: A significant increase in CA-HIV-RNA (P = 0.049) and HIV DNA (P = 0.042) was observed 24 h after each infusion of anti-PD-1 monoclonal antibody. The Z-score for IL-6 increased from −0.46 ± 0.53 to 0.28 ± 0.78 at 24 h after infusion (P = 0.02), and further increased to 0.61 ± 1.0 at 7 days after each infusion (P = 0.007). A significant correlation was observed between IL-6 and HIV DNA (P = 0.02). Conclusion: The CA-HIV-RNA, HIV DNA, and IL-6 levels significantly increased after infusion of anti-PD-1 monoclonal antibody in the three HIV-infected patients with NSCLC. These results support an early transient effect of anti-PD-1 monoclonal antibody infusion on HIV reservoirs. However, the long-term effect needs to be investigated in a larger cohort with a longer follow-up period.