The Impact of HIV on the Tumor Microenviornment and Survival in Colorectal Cancer Patients in South Africa

PROJECT SUMMARY People living with HIV (PWLH) now have improved access to highly effective anti-retroviral therapy (ART), leading to an aging global population with HIV. This aging population is experiencing a higher incidence of chronic and age-related diseases, including cancer. Non–AIDS-defining cancers are now the leading non-AIDS cause of death in PLWH. Colorectal cancer (CRC) is the fourth most diagnosed cancer worldwide, and prevalence among PLWH is increasing. Studies conducted in the US show that PLWH are less likely than others to receive curative-intent cancer treatment for CRC and have worse cancer-specific and overall mortality, even when accounting for treatment disparities. These findings suggest an underlying biological difference between colorectal tumors that develop in people with and without HIV, but few studies have tested this hypothesis. In the proposed study we will collaborate with investigators at the University of KwaZulu-Natal in KwaZulu-Natal, South Africa, a province with a high HIV prevalence rate, especially in the Black African population (27.2% among those ages 15-48 years). Using an existing database, we will conduct a retrospective review of patients with (n=145) and without (n=290) HIV who were diagnosed with CRC in KwaZulu-Natal province between 2000-2020. The goal of this study is to determine how the presentation of CRC differs in the population with and without HIV, whether PLWH experience cancer-treatment disparities, and how overall and cancer-specific survival differs by HIV status. This study will be one of the first to examine the effect of HIV on CRC in an HIV-endemic population. Further, we will obtain pathology slides from patients with CRC with (n=25) and without (n=25) HIV who completed curative-intent treatment for localized CRC and compare characteristics of the tumor microenvironment (TME) by HIV status. Based on preliminary data in women with breast cancer with and without HIV, we hypothesize that we will observe increased T-cell density in the TME of cancers from people with HIV, compared to those without HIV, but that there will be increased markers of T-cell exhaustion. In future studies we will examine whether differences in the TME may explain disparities in cancer-specific and overall survival between people with and without HIV and CRC.