Mitochondrial DNA impairment in nucleoside reverse transcriptase inhibitor-associated cardiomyopathy

Acquired immune deficiency syndrome (AIDS) is a global epidemic that continues to escalate. Recent World Health Organization estimates include over 33 million people currently diagnosed with HIV/AIDS. Another 20 million HIV-infected individuals died over the past quarter century. Antiretrovirals are effective treatments that changed the outcome of HIV infection from a fatal disease to a chronic illness. Cardiomyopathy (CM) is a bona fide component of HIV/AIDS with occurrence that is higher in HIV positive individuals. CM may result from individual or combined effects of HIV, immune reactions, or toxicities of prolonged antiretrovirals. Nucleoside reverse transcriptase inhibitors (NRTIs) are the cornerstone of antiretroviral therapy. Despite pharmacological benefits of NRTIs, NRTI side effects include increased risk for CM. Clinical observations and in vitro and in vivo studies support various mechanisms of CM. This perspective highlights some of the hypotheses and focuses on mitochondrial-associated pathways of NRTI- related CM.