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Identification of Immune Biomarkers That Associate With HIV Disease Pathogenesis: Kaposi Sarcoma and Substance Abuse
The widespread initiation of antiretroviral therapy has allowed people living with HIV (PLWH) to live more standard lives. As PLWH are aging, they are increasingly at risk for developing comorbidities at younger ages compared to the general population. Many environmental and behavioral factors, as well as co-infections, have significant impacts on PLWH. The objective of this research was to investigate the immune response in PLWH and identify immune biomarkers that associate with HIV disease pathogenesis. Two parallel studies were conducted to accomplish this objective: (1) quantification of the humoral immune response against Kaposi sarcoma-associated herpesvirus (KSHV) and (2) analysis of the combinatorial effects of injection drug use (IDU) and HIV infection on systemic inflammation. To generate a high-resolution map of the anti-KSHV humoral immune response, VirScan was employed. VirScan is a phage library that displays 56-mer peptides systematically scanning across the KSHV proteome. We quantified the antibody repertoires against this KSHV peptidome and compared them between KS patients and asymptomatic KSHV-seropositive individuals. We detected consistently targeted epitopes within the immunodominant proteins, found that the magnitude of the antibody response was increased in KS and decreased in the context of HIV co-infection, and identified a subset of 25 peptide-level antibody responses that could discriminate between KS patients and asymptomatic individuals. To analyze the combinatorial effects of IDU and HIV infection, we quantified the levels of 74 inflammatory mediators and 37 immune cell populations across four groups: controls, HIV-/IDU+, HIV+/IDU-, and HIV+/IDU+. We found that all three HIV/IDU groups were significantly different from controls, but few pairwise differences between the mono- and dual-affected groups were detected. A lack of significant synergistic effects between HIV infection and IDU reinforced this finding and highlighted the remarkable similarities between PLWH and people who inject drugs, regardless of HIV co-infection. Overall, the comprehensive immune profiling conducted during this research has provided vital contributions to understanding the interplay between HIV infection and its comorbidities and cofactors: KS and IDU.
Bennett, Sydney J, "Identification of Immune Biomarkers That Associate With HIV Disease Pathogenesis: Kaposi Sarcoma and Substance Abuse" (2023). ETD collection for University of Nebraska - Lincoln. AAI30575675.