Sustained Activation of Myeloperoxidase Is Associated with Oxidative Stress and Inflammation in People Living with the Human Immunodeficiency Virus at Risk of Cardiovascular Disease

People living with the human immunodeficiency virus (PLWH) are continually subjected to challenges involving the development of non-acquired immunodeficiency syndrome (AIDS)-related comorbidities despite the effectiveness of highly active antiretroviral therapy (HAART). Exacerbated oxidative stress, which is intrinsically linked to chronic inflammation, is implicated in non-AIDS comorbidities, including the increased risk of cardiovascular disease (CVD) observed in PLWH. Here, we review evidence on the potential pathological implications of myeloperoxidase (MPO), a leukocyte-derived enzyme and a key mediator of oxidative stress and inflammation, in driving CVD-related complications in PLWH. A systematic review approach was taken to identify relevant clinical studies through searches of Cochrane Libraries, PubMed, Web of Science, ScienceDirect, and Google Scholar, up to the 30 June 2025. The summarized data appraised clinical studies (n = 14) on adults (n = 1445) with a mean age of 45 years reporting on the association between MPO and enhanced lipid peroxidation marked by elevated concentrations of oxidized low-density lipoprotein cholesterol (oxLDL-C) in PLWH. Such results were consistent with elevated inflammatory markers, including high sensitivity C-reactive protein (hsCRP), which was also linked with endothelial dysfunction. There is a lack of evidence linking the duration of HAART to MPO levels or an increased risk of CVD. However, there is room to explore whether enhanced levels of oxLDL-C, in association with sustained MPO activation, could drive CVD risk in PLWH. The present review provides essential information on the pathological relevance of MPO in endothelial dysfunction and CVD risk in PLWH.