Current topics in HIV pathogenesis, part 2: Inflammation drives a Warburg-like effect on the metabolism of HIV-infected subjects

• Inflammation, inflammasome and innate immunity plays a key role in stimulating metabolism, and vice versa.
• HIV-1 infection is characterized by the activation of NLRP3-inflammasome and elevated inflammation that are fuelled by bacterial translocation and dysbiosis.
• Inflammation and excessive metabolism during HIV-1 infection are not restored by ART.
• Inflammation-related deregulation of metabolism in HIV-1-infected subjects results in a number of heath complications.

HIV-1 infection leads to a depletion of CD4 T-cells associated with a persistent immune inflammation and changes in cellular metabolism. Most effort of managing HIV infection with combination of antiretroviral therapies (ART) has been focused on CD4 T-cell recovery, while control of persistent immune inflammation and metabolism were relatively underappreciated in the past. Recent discoveries on the interplay between innate immunity, inflammation (especially the inflammasome) and metabolic changes in the context of cancer and autoimmunity provide an emerging field for chronic viral infections including HIV-1. In a previous review, we described the deregulated metabolism contributing to immune dysfunctions such as alteration of memory T-cell responses, mucosal protection, and dendritic cell-related antigen presentation. Here, we summarize the latest knowledge on the detrimental influence of long-lasting inflammation and inflammasome activation induced by HIV-1, gut dysbiosis, and bacterial translocation, on metabolism during the course of viral infection. We also report on the inability of ART to fully counteract inflammation, resulting in partial metabolic improvement and leading to an insufficient decrease in the risk of non-AIDS events. Further advances in our understanding of the relationship between inflammation, altered metabolism, and long-term ART is warranted. Additionally, there is a critical need for developing new strategies to regulate the pro-inflammatory signals to enhance cellular metabolism and immune functions in order to improve the quality of life of individuals living with HIV-1.