A Critical Review of the Biochemical Mechanisms and Epigenetic Modifications in HIV- and Antiretroviral-Induced Metabolic Syndrome

Abstract

Metabolic syndrome (MetS) is a non-communicable disease characterised by a cluster of metabolic irregularities. Alarmingly, the prevalence of MetS in people living with Human Immunodeficiency Virus (HIV) and antiretroviral (ARV) usage is increasing rapidly. This study aimed to look at biochemical mechanisms and epigenetic modifications associated with HIV, ARVs, and MetS. More specifically, emphasis was placed on mitochondrial dysfunction, insulin resistance, inflammation, lipodystrophy, and dyslipidaemia. We found that mitochondrial dysfunction was the most common mechanism that induced metabolic complications. Our findings suggest that protease inhibitors (PIs) are more commonly implicated in MetS-related effects than other classes of ARVs. Furthermore, we highlight epigenetic studies linking HIV and ARV usage to MetS and stress the need for more studies, as the current literature remains limited despite the advancement in and popularity of epigenetics.

The Potential of Spirulina platensis to Ameliorate the Adverse Effects of Highly Active Antiretroviral Therapy (HAART)

“…Recent reports have linked some HIV-related features to MetS. These characteristic features include escalated cases of cardiovascular diseases, type 2 diabetes mellitus, dyslipidemia, immunodeficiency, high viral load, and atherosclerosis [ 7 ]. Recently, studies have suggested that HAART, in addition to the above-mentioned HIV-related features, actively induces MetS in persons with HIV [ 7 , 39 , 40 , 41 ].…”

“…These characteristic features include escalated cases of cardiovascular diseases, type 2 diabetes mellitus, dyslipidemia, immunodeficiency, high viral load, and atherosclerosis [ 7 ]. Recently, studies have suggested that HAART, in addition to the above-mentioned HIV-related features, actively induces MetS in persons with HIV [ 7 , 39 , 40 , 41 ]. Earlier studies by Palios et al (2011) on arterial stiffness, displayed by pulse wave velocity (PWV), and markers of MetS, reported that persons with HIV exhibited an increased degree of PWV when compared with the healthy controls.…”

“…Despite its success in prolonging HIV-infected patients’ lifespans, the use of HAART promotes metabolic syndrome (MetS) through an inflammatory pathway, excess production of reactive oxygen species (ROS), and mitochondrial dysfunction. Over three decades since its discovery, HAART has significantly improved the diagnosis and management of persons with HIV [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. The persistence of MetS before and during HAART treatment further highlights the need for more studies on MetS inhibitory compounds, such as Spirulina platensis (SP) [ 13 ], Moringa oleifera [ 14 , 15 ], Curcumin [ 16 ], and Mangiferin [ 17 ].…”

Roles of Interleukin-6-mediated immunometabolic reprogramming in COVID-19 and other viral infection-associated diseases

“…Small-molecule inhibitors targeting PI3 kinase VPS34 or fatty acid metabolism have been shown to inhibit SARS-CoV-2 activity [77] . HIV infection in adulthood is more likely to cause metabolic syndrome, which includes excess abdominal fat, abnormal blood sugar and lipid levels, and high blood pressure, as well as an increased risk of diabetes, heart disease, and stroke [78] , [79] . All of these are attributable to HIV itself, inflammation, and side effects of antiretroviral therapy [79] .…”

“…HIV infection in adulthood is more likely to cause metabolic syndrome, which includes excess abdominal fat, abnormal blood sugar and lipid levels, and high blood pressure, as well as an increased risk of diabetes, heart disease, and stroke [78] , [79] . All of these are attributable to HIV itself, inflammation, and side effects of antiretroviral therapy [79] . AIDS-related inflammation and immune activation also occur throughout the infection and treatment process, which is related to the persistence of HIV, translocation of intestinal flora, reduction of regulatory T cells, and combination or secondary infection with other viruses [80] , [81] .…”