학술논문
Impact of Anti PD-1 Immunotherapy on HIV Reservoir and Anti-Viral Immune Responses in People Living with HIV and Cancer.
Document Type
Article
Author
Baron, Marine; Soulié, Cathia; Lavolé, Armelle; Assoumou, Lambert; Abbar, Baptiste; Fouquet, Baptiste; Rousseau, Alice; Veyri, Marianne; Samri, Assia; Makinson, Alain; Choquet, Sylvain; Mazières, Julien; Brosseau, Solenn; Autran, Brigitte; Costagliola, Dominique; Katlama, Christine; Cadranel, Jacques; Marcelin, Anne-Geneviève; Lambotte, Olivier; Spano, Jean-Philippe
Source
Subject
*EPSTEIN-Barr virus
*HIV-positive persons
*PROGRAMMED cell death 1 receptors
*IMMUNE response
*HIV
*IMMUNE checkpoint proteins
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Language
ISSN
2073-4409
Abstract
The role of immune checkpoints (ICPs) in both anti-HIV T cell exhaustion and HIV reservoir persistence, has suggested that an HIV cure therapeutic strategy could involve ICP blockade. We studied the impact of anti-PD-1 therapy on HIV reservoirs and anti-viral immune responses in people living with HIV and treated for cancer. At several timepoints, we monitored CD4 cell counts, plasma HIV-RNA, cell associated (CA) HIV-DNA, EBV, CMV, HBV, HCV, and HHV-8 viral loads, activation markers, ICP expression and virus-specific T cells. Thirty-two patients were included, with median follow-up of 5 months. The CA HIV-DNA tended to decrease before cycle 2 (p = 0.049). Six patients exhibited a ≥0.5 log10 HIV-DNA decrease at least once. Among those, HIV-DNA became undetectable for 10 months in one patient. Overall, no significant increase in HIV-specific immunity was observed. In contrast, we detected an early increase in CTLA-4 + CD4+ T cells in all patients (p = 0.004) and a greater increase in CTLA-4+ and TIM-3 + CD8+ T cells in patients without HIV-DNA reduction compared to the others (p ≤ 0.03). Our results suggest that ICP replacement compensatory mechanisms might limit the impact of anti-PD-1 monotherapy on HIV reservoirs, and pave the way for combination ICP blockade in HIV cure strategies. [ABSTRACT FROM AUTHOR]