Role of Mitochondria in HIV Infection and Associated Metabolic Disorders: Focus on Nonalcoholic Fatty Liver Disease and Lipodystrophy Syndrome

P Pérez-Matute,L Pérez-Martínez,J A Oteo,J R Blanco

doi:10.1155/2013/493413

Abstract

Highly active antiretroviral therapy (HAART) has considerably improved the prognosis of HIV-infected patients. However, prolonged use of HAART has been related to long-term adverse events that can compromise patient health such as HIV-associated lipodystrophy syndrome (HALS) and nonalcoholic fatty liver disease (NAFLD). There is consistent evidence for a central role of mitochondrial dysfunction in these pathologies. Nucleotide reverse transcriptase inhibitors (NRTIs) have been described to be mainly responsible for mitochondrial dysfunction in adipose tissue and liver although nonnucleoside transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs) have also showed mitochondrial toxicity, which is a major concern for the selection and the long-term adherence to a particular therapy. Several mechanisms explain these deleterious effects of HAART on mitochondria, and evidence points to other mechanisms beyond the “Pol-γ hypothesis.” HIV infection has also direct effects on mitochondria. In addition to the negative effects described for HIV itself and/or HAART on mitochondria, HIV-infected patients are more prone to develop a premature aging and, therefore, to present an increased oxidative state that could lead to the development of these metabolic disturbances observed in HIV-infected patients.

Highlights

HIV Infection and Antiretroviral TherapyHuman immunodeficiency virus (HIV) infection is a serious public health disorder that affects up to 34 million people in the world [1]
Active antiretroviral therapy (HAART) has considerably improved the prognosis of Human immunodeficiency virus (HIV)-infected patients
The underlying mechanisms that could explain the relationship between mitochondrial dysfunction and HIV, NASH, or HIV-associated lipodystrophy syndrome (HALS) are not fully understood despite accumulating evidence points to other mechanisms beyond the Pol-γ hypothesis

Summary

HIV Infection and Antiretroviral Therapy

Human immunodeficiency virus (HIV) infection is a serious public health disorder that affects up to 34 million people in the world [1]. The introduction of highly active antiretroviral therapy (HAART) has considerably improved the prognosis of HIV-infected patients leading to a significant reduction of HIV-related morbidity and mortality [3]. For these reasons, HIV infection is nowadays considered “just” a chronic infection. Prolonged use of HAART has been related to long-term adverse events that can compromise patient health These deleterious effects have been reported for the majority of antiretroviral drugs and are the most common causes for therapy discontinuation. Several studies have demonstrated mitochondrial impairment in HIV-infected patients and especially in those suffering from HALS or fatty liver, suggesting a pivotal role of mitochondria dysfunction in the pathophysiology of these alterations. We describe the role of oxidative stress in HIV infection and how different compounds with antioxidant capacities have been studied in an attempt to decrease this oxidative state in a way to ameliorate the deleterious effects of HIV-infection and its metabolic associated disorders

HIV and Mitochondria

Role of Mitochondria in HIV-Associated Fatty Liver Disease

Role of Mitochondria in HIV-Associated Lipodystrophy Syndrome

HIV and Oxidative Stress

Findings

Concluding Remarks