Is HIV-Associated Mitochondrial Dysfunction (HIVAMD) Related to Weight Gain and Metabolic Complications on PLWH? Contribution of Ultra-processed Foods (ULPs)

Abstract

Introduction With the advent of antiretroviral therapy (ART), HIV has transitioned from a fatal disease to a chronic condition, enabling people living with HIV (PLWH) to achieve life expectancies similar to those of the general population. However, PLWH experience higher rates of non-AIDS-related illnesses, particularly metabolic diseases such as insulin resistance, fatty liver, and metabolic syndrome. These conditions, collectively referred to as “inflammaging,” are attributed to chronic inflammation and immune activation, but their underlying causes remain debated. This review explores the role of ultra-processed foods (UPFs) in exacerbating HIV-associated mitochondrial dysfunction (HIVAMD) and its impact on weight gain and metabolic complications. Methods The review examines existing literature on the impact of ART on metabolic health in PLWH, differentiating between lipohypertrophy and obesity. It investigates the proposed mechanisms linking ART to metabolic dysregulation, including the effects of UPFs, especially fructose, on mitochondrial function. Data on insulin resistance, hyperinsulinemia, microbial translocation, and the potential exacerbation of these conditions by UPFs are synthesized to propose a comprehensive model. Results ART, particularly integrase strand transfer inhibitors (INSTIs), has been associated with increased visceral adipose tissue (VAT) and metabolic syndrome. Proposed mechanisms include ART-induced alterations in appetite regulation, insulin signaling, and energy expenditure. HIVAMD is identified as a key factor in metabolic complications, with UPFs contributing to mitochondrial dysfunction, insulin resistance, and microbial translocation. Fructose overconsumption is highlighted for its role in liver inflammation, fatty liver, and metabolic syndrome through mechanisms such as ATP depletion, NAD+ depletion, and oxidative stress. Conclusion PLWH are at increased risk of metabolic complications due to the combined effects of HIVAMD and the consumption of UPFs. Addressing these issues requires prospective clinical trials to evaluate dietary interventions and nutritional supplements. Lifestyle modifications, such as intermittent fasting and pharmacological measures, may mitigate these complications. Community-based research initiatives are essential for developing and implementing effective interventions to improve the metabolic health of PLWH.