The present invention relates to the discovery that measurement of the level of cytochrome c (Cyt-C) in the plasma can be used as a diagnostic signature to predict antiretroviral therapy (ART) toxicity in human immunodeficiency virus (HIV) infected patients. Thus, in various embodiments described herein, the methods of the invention relate to methods of diagnosing a HIV patient with ART toxicity, methods of predicting a patient's risk of having or developing toxicity for ART, methods of assessing if a patient will benefit from a change in the treatment strategies by adjusting the dosage and/or changing the medication or even terminating of ART, and methods of predicting antiretroviral drugs propensity for causing mitochondrial toxicity. Furthermore, the invention encompasses a diagnostic kit for carrying out the aforementioned methods.