1. Persistently Elevated Expression of Systemic, Soluble Co-Inhibitory Immune Checkpoint Molecules in People Living with HIV before and One Year after Antiretroviral Therapy.
- Author
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Labuschagne Naidoo, Robyn-Brooke, Steel, Helen C., Theron, Annette J., Anderson, Ronald, Tintinger, Gregory R., and Rossouw, Theresa M.
- Subjects
IMMUNE checkpoint proteins ,HEPATITIS A virus cellular receptors ,CYTOTOXIC T lymphocyte-associated molecule-4 ,PROGRAMMED cell death 1 receptors ,PROGRAMMED death-ligand 1 - Abstract
Introduction: Increasing drug resistance and the absence of a cure necessitates exploration of novel treatment strategies for people living with HIV (PLWH). Targeting of soluble co-inhibitory immune checkpoint molecules (sICMs) represents a novel, potentially effective strategy in the management of HIV. Methods: In this retrospective, longitudinal, observational study, the plasma levels of five prominent co-inhibitory sICMs—CTLA-4, LAG-3, PD-1 and its ligand PD-L1, as well as TIM-3—were quantified in 68 PLWH—before and one year after antiretroviral therapy (ART)—and compared with those of 15 healthy control participants. Results: Relative to control participants, PLWH had substantially elevated pre-treatment levels of all five co-inhibitory sICMs (p < 0.0001–p < 0.0657), which, over the 12-month period of ART, remained significantly higher than those of controls (p < 0.0367–p < 0.0001). PLWH with advanced disease, reflected by a CD4+ T cell count <200 cells/mm
3 before ART, had the lowest levels of CTLA-4 and LAG-3, while participants with pre-treatment HIV viral loads ≥100,000 copies/mL had higher pre-treatment levels of TIM-3, which also persisted at 12 months. Conclusions: Plasma levels of CTLA-4, LAG-3, PD-1, PD-L1 and TIM-3 were significantly elevated in treatment-naïve PLWH and remained so following one year of virally-suppressive ART, possibly identifying LAG-3 and TIM-3 in particular as potential targets for adjuvant immunotherapy. [ABSTRACT FROM AUTHOR]- Published
- 2024
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