Abstract
Since the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months). Body weights and weight gain, blood metabolite levels (total cholesterol, HDL, LDL, triglycerides), echocardiography and cardiac mitochondrial respiration were assessed in PI-treated rats ± various co-treatments. Our data reveal that PI treatment significantly lowered body weight and cardiac respiratory function while no significant changes were found for heart function and blood metabolite levels. Moreover, all co-treatments ameliorated the PI-induced decrease in body weight after 4 months of PI treatment, while RSV co-treatment enhanced cardiac mitochondrial respiratory capacity in PI-treated rats. This pilot study therefore provides novel hypotheses regarding RSV co-treatment that should be further assessed in greater detail.
Highlights
The human immunodeficiency virus (HIV) has become a global pandemic over the last 30 years, affecting ~34 million people (2010), of which 2.7 million were children under the age of 15 years old [1]
Our findings show that RSV in particular elicited beneficial outcomes by reversing protease inhibitors (PIs)-mediated weight changes and enhancing cardiac mitochondrial respiratory function
In order to determine whether the various treatments induced any gross anatomical changes, body weight and weight gain were determined together with weights for harvested organs—normalized to tibial length
Summary
The human immunodeficiency virus (HIV) has become a global pandemic over the last 30 years, affecting ~34 million people (2010), of which 2.7 million were children under the age of 15 years old [1] It began as a relatively insignificant disease during the 1980s, HIV prevalence has since escalated to become one of the leading, global causes of morbidity and PLOS ONE | DOI:10.1371/journal.pone.0170344. The incidence of cardiovascular complications in this population group has begun to increase [8], usually manifesting relatively late during disease progression [8,9] It remains unclear whether such effects are due to the virus itself and/or ARV treatment [7]
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