Inflammation is a crucial component of the immune response essential for host defense and tissue repair. However, when the immune response becomes dysregulated, it can contribute to the pathogenesis of chronic diseases. While acute inflammation is a short-lived, protective response, chronic inflammation is sustained over time and can lead to immune dysfunction, tissue damage, and disease progression. The chronic inflammation theory of disease suggests that persistent immune activation/inflammation underlies both infectious and non-infectious conditions and serves as a unifying mechanism across distinct pathological states. In this review article, we argue that human immunodeficiency virus (HIV) infection represents a prime model for studying chronic inflammation, and that despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) exhibit persistent immune activation, systemic inflammation, and an increased risk of cardiovascular, metabolic, and neurodegenerative diseases. Here, the interplay between microbial translocation, immune dysregulation, and metabolic reprogramming fuels a state of chronic inflammation that accelerates disease progression beyond HIV itself. Key factors such as T-cell exhaustion, persistent monocyte/macrophage activation, and immunometabolic dysfunction contribute to such a sustained inflammatory state. This review explores the molecular and cellular mechanisms driving chronic inflammation in HIV infection with a focus on immunometabolism and its implications for broader inflammatory diseases. By understanding such pathways, we can identify novel therapeutic targets to mitigate inflammation-driven disease progression not only in HIV but across a spectrum of chronic inflammatory conditions.