Background: Muscle mitochondrial dysfunction associated with HIV and antiretroviral therapy (ART) may improve with exercise.Methods: Muscle specimens obtained before and after 24 weeks of exercise in older people with HIV (PWH; n = 18; ART >2 years) and uninfected controls (n = 21) were analyzed for citrate synthase (CS) activity and complexes (C) I-V, manganese superoxide dismutase (MnSOD), peroxisome proliferator-activated receptor-γ coactivator-1 (PGC1α), and voltage-dependent anion channel 1 (VDAC1) content.Results: Only controls had increased CS, MnSOD, PGC1α, and CIV (P ≤ .01; P < .01 vs PWH) after training.Conclusions: The blunted mitochondrial adaptations to training in PWH suggests the need for different types of exercise-induced stimulation.Clinical Trials Registration: NCT02404792. [ABSTRACT FROM AUTHOR]