Th17, gut, and HIV: therapeutic implications

Abstract

The purpose of this review is to discuss the apparent impact of persistent-immune activation and inflammation on morbidity and mortality among treated HIV-infected individuals, to explore the potential role of Th17 T-cell depletion in this process, and to discuss potential-therapeutic implications. Although the vast majority of HIV-infected individuals can now achieve and maintain viral suppression with modern-antiretroviral therapy (ART), their life expectancy remains much shorter than the general population and they continue to be at much higher risk for non-AIDS-associated diseases commonly associated with aging (non-AIDS-associated cancer, cardiovascular disease, etc). Abnormal levels of immune activation and inflammation persist despite sustained viral suppression and may drive these clinical events. Although the causes of persistent-immune activation remain incompletely characterized, persistent low-level HIV replication and/or release from latently infected cells in gut-associated lymphoid tissue (GALT) and microbial translocation probably play a major role. Failure to restore Th17 cells in GALT during ART might impair both the recovery of the gut mucosal barrier and the clearance of microbial products. Insights from recent-pathogenesis studies might suggest novel-therapeutic approaches designed to restore Th17 cells in GALT, thereby decreasing microbial translocation, immune activation, and ultimately morbidity and mortality during treated HIV infection.