Insulin resistance, lipodystrophy and cardiometabolic syndrome in HIV/AIDS

Abstract

HIV associated insulin resistance, lipodistrophy and cardiometabolic syndrome have been extensively studied and continue to be the scope of much research. There is compelling evidence that both the HIV itself and the therapeutical regimes are major contributors to all of these associated comorbidities. HIV has increasingly been recognized as a disease of accelerated aging, manifested by increased progression of vascular disease and cellular markers of aging. The antiretroviral medication can increase insulin resistance and cause lipotoxocity and HIV-associated lipodystrophy leading to cardiovascular pathology. In this article we review the pathogenesis, management, and prevention of the long-term complications of HIV and its therapies, including cardiovascular disease, lipodystrophy, and insulin resistance along with the growing focus on biomarkers to predict development of end-organ disease. Through a focused literature search we review the established evidence, the developing research about the treatment strategies in treated HIV infection as well as identify potential areas for future research.

Metabolic complications and selected cytokines in HIV‑infected individuals

“…24 An increased serum FFA concentration is related to the degree of insulin resistance, as FFAs have been proposed to induce skeletal muscle insulin resistance. 17,25 Our results confirm the observation that HIV itself induces lipid metabolic changes, which makes patients more vulnerable to the side effects of ARV.…”

“…21 It can be partially explained by the fact that those abnormalities are more common in ethnic minorities than in Caucasians. 17 We observed a correlation between the duration of ARV therapy and the risk of metabolic disturbances. Patients who received the therapy for more than 2 years had a significant decrease of RMR.…”

Dysregulation of Endoplasmic Reticulum Stress and Autophagic Responses by the Antiretroviral Drug Efavirenz

“…With increased survival, it is estimated that patients aged 50 years and older represent approximately 50% of all HIV-infected individuals in the United States (Vance, 2010). In these long-term survivors, the infection itself is controlled, but several pathologies are observed, such as cardiovascular, lipid, metabolic, and neurologic disorders (Clifford and Ances, 2013;Deeks et al, 2013;Galescu et al, 2013;Kebodeaux et al, 2013;Lake and Currier, 2013). Before the advent of cART, neurologic disorders in HIV patients were often associated with severe cognitive dysfunction, such as HIV-associated dementia.…”

Harveian Oration 2016: Some observations on the causes and consequences of obesity

“…It is increasingly recognised, at least in a partial form, as a consequence of total body irradiation for certain childhood cancers, 90 and of chronic antiviral therapy for HIV infection. 91 What characterises all generalised forms of lipodystrophy, whatever their causes, is the early development of insulin resistance, dyslipidaemia and fatty liver reminiscent of an aggressive version of more typical 'metabolic syndrome'. Indeed, there is no feature of the metabolic syndrome, including increased risks of atherosclerosis and severe fatty liver disease, that is not reliably present in patients with lipodystrophy.…”