Metabolic alterations in immune cells have been shown to impact how they function1. Much of the literature surrounding host metabolism, and specifically T cell metabolism, during viral infection has examined the role of glycolysis, as increased glycolysis is a hallmark of inflammatory cells2. Following viral infection, T cells have a marked increase in glucose uptake and glycolytic rate3, and glycolysis is required for effector functions, such as cytokine production2. However, the role of oxidative phosphorylation (OXPHOS) in viral infection is much less well defined. HIV-1 infection has been shown to reprogram the metabolism of immune cells, upregulating almost all branches of metabolism, including glucose, lipid and tryptophan metabolism4 and OXPHOS. The molecular mechanisms behind the increase in OXPHOS and its role in disease outcome are unknown. In the current issue of Nature Immunology, Guo et al.5 have now elucidated one mechanism contributing to increases in OXPHOS and have demonstrated that this pathway is positively correlated with peak viremia and a worse disease outcome. Furthermore, they have demonstrated that these increases in OXPHOS can be dampened in human cells and humanized mice with the widely available drug metformin, reducing viremia and T cell depletion in humanized mouse models, which points to metformin as a possible therapy in HIV-1 infection.