Review
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World J Clin Infect Dis. Nov 25, 2013; 3(4): 47-57
Published online Nov 25, 2013. doi: 10.5495/wjcid.v3.i4.47
Microbial translocation, residual viremia and immune senescence in the pathogenesis of HIV-1 infection
Alessandra Fantauzzi, Francesca Falasca, Gabriella d’Ettorre, Eugenio Nelson Cavallari, Ombretta Turriziani, Vincenzo Vullo, Ivano Mezzaroma
Alessandra Fantauzzi, Ivano Mezzaroma, Department of Clinical Medicine, University of Rome, 00185 Rome, Italy
Francesca Falasca, Ombretta Turriziani, Department of Molecular Medicine, University of Rome, 00169 Rome, Italy
Gabriella d’Ettorre, Eugenio Nelson Cavallari, Vincenzo Vullo, Department of Public Health and Infectious Diseases, University of Rome, 00185 Rome, Italy
Author contributions: All of the authors contributed equally to this study.
Correspondence to: Ivano Mezzaroma, MD, Department of Clinical Medicine, University of Rome, Viale dell’Università 37, 00185 Rome, Italy. ivano.mezzaroma@uniroma1.it
Telephone: +39-06-4463328 Fax: +39-06-4440806
Received: July 19, 2013
Revised: November 2, 2013
Accepted: November 15, 2013
Published online: November 25, 2013
Abstract

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 cART-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.

Keywords: Human immunodeficiency virus-1, Combined antiretroviral therapy, Immune activation, Microbial translocation, Residual viremia, Immune senescence

Core tip: The aim of this review was to summarize the most relevant mechanisms in human immunodeficiency virus-1 pathogenesis by focusing on the role of microbial translocation, residual viremia, and immune senescence or “inflammaging” in disease progression to full-blown AIDS. Moreover, the impact of antiretroviral therapy on these mechanisms was investigated.