HIV and Malignancies

The vast majority of HIV-infected individuals can now achieve and maintain undetectable viral load on antiretroviral therapy. However, HIV-infected individuals continue to be at higher risk for non-AIDS associated complications including malignancies which now account for the majority of deaths. Population-based epidemiologic studies have supported the finding that colorectal cancer (CRC) is significantly elevated in HIV-infected individuals compared to the general population. Persistent immune activation and inflammation, mediated by gut mucosal inflammation, have been proposed as important mechanisms of non-AIDS associated complications and accelerated aging. Indeed, increased gut epithelial turnover is observed in macaques with chronic SIV infection. A mucosal inflammatory milieu in combination with immunodeficiency likely represents dual mechanisms contributing to carcinogenesis. As such, the specific aims of this study are (1) to confirm that colorectal neoplasms are increased in HIV-infected individuals compared to the general population during screening and surveillance colonoscopy and (2) to assess whether increases in epithelial cell turnover, proliferation, and apoptosis results in an increased risk for development of adenoma and (3) characterize differences in colorectal neoplasms/cancers among HIV-infected and uninfected individuals. The results of this study will have important clinical implications for tailoring CRC screening and surveillance guidelines and may also serve as a model for understanding the role of an inflammatory microenvironment and carcinogenesis.