The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide(LPS) levels, which are used as an indicator of microbial translocation(MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the systemic circulation has been described as a driver of immune activation. In contrast, comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of HIV-1 disease. We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV-1 infection:(1) MT;(2) the role of residual viremia; and(3) “immune senescence” or “inflammaging.” Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 pathogenesis. Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression. The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1 (HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide (LPS) levels, which are used as an indicator of microbial translocation (MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the total circulation; comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of H We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV -1 infection: (1) MT; (2) the role of residual viremia; and (3) “immune senescence” or “inflammaging. ” Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression.