(P123) Effect of HIV infection on immune cell substrate utilization and mitochondrial homeostasis

Background: The optimal functioning of immune cells depends on a robust and adaptable metabolic program powered by dynamic mitochondrial activity. Immunometabolism has become an attractive immunotherapeutic strategy, particularly in chronic HIV infection.

Objective: To investigate the metabolic functionality of different human leukocyte populations in chronic HIV infection with combination antiretroviral therapy (cART).

Methods: Sixteen female volunteers with chronic HIV infection managed by long-term cART and fifteen HIV-uninfected female volunteers were recruited. The uptake of glucose and fats, as well as the mitochondrial mass and mitochondrial potential, were measured in PBMCs using flow cytometry.

Results: During chronic HIV infection, cellular uptake of glucose increases in innate immune cells while having little effect on adaptive immune cells. In particular, HIV+ dendritic cells have a higher glucose uptake than other profiled cell types. There was a negative correlation between CD4 counts, which decline with HIV infection, and glucose uptake in HIV+ patients. CD4+ T-cells had the lowest uptake of fats compared to all other cells regardless of HIV status, while CD8+ T-cells took up more fatty acids. Despite the lower utilization of glucose and fats in CD4+ T-cells, the mitochondrial mass increased in HIV+ CD4+ T-cells compared to HIV- CD4+ T-cells controls. They also had the highest mitochondrial potential.

Discussions: Mitochondrial activity was higher in adaptive immune cells than in innate immune cells. However, despite an increase in mitochondrial mass and potential in HIV-infected CD4+ T-cells, these cells still had the lowest metabolic utilization of glucose and fats. This suggests that in chronic HIV, CD4+ T-cells may be maladapted to the use of common substrates for glycolysis and OXPHOS or may prefer an alternative fuel source.

Relevance: This study provides new insights into the metabolic changes in human leukocyte populations during chronic HIV infection and cART and how this may affect their ability to fight off infections. The findings of this study are relevant for the field of sexually transmitted infections (STI) as they provide a deeper understanding of the immune system's response to chronic viral infections and how this may impact the immune response.