Graduation Date

Fall 12-20-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Epidemiology

First Advisor

Christine M. Arcari

Second Advisor

Ted Cieslak

Third Advisor

Paul Levine

Fourth Advisor

Jane L. Meza

Abstract

The burden of cancers not previously associated with an HIV infection, called non-AIDS defining cancers (NADCs), have increased in the years since highly active anti-retroviral therapy has been introduced. The studies in this dissertation attempted to quantify this burden via incidence and mortality compared to the general population. Further, an assessment of risk factors and creation of a predictive risk model, a nomogram, were utilized to better understand how factors associated with demographics, lifestyle, and immune response affected risk for an NADC diagnosis once therapy was initiated and HIV better controlled. Standardized incidence and mortality ratios showed that burden of NADC is much higher among HIV-infected persons, and especially among those cancers with a viral etiology such as anal cancer (SIR: 312.2; SMR: 347.2), Hodgkin’s lymphoma (SIR: 97.5; SMR: 140.8), and liver cancer (SIR: 30.9; SMR: 35.5). NADCs not associated with a viral etiology were also increased including lung cancer (SIR: 14.3; SMR: 17.0) and melanoma (SIR: 6.2; SMR: 11.0). Multivariate cox regression for viral associated NADCs found that age (HR: 2.71; 95% CI: 1.84-3.98), prior AIDS-defining infection (HR: 1.42; 95% CI: 1.04-1.93), and Hepatitis B (HR: 2.44; 95% CI: 1.68-3.55) increased risk. Risk for non-viral associated NADCs increased with older age (HR: 12.8; 95% CI: 8.57-19.1) and tobacco use (HR: 1.3; 95% CI: 1.07-1.60). The nomogram had average ability to predict a person’s chance of developing a viral- or non-viral associated NADCs (c-index of 0.466 and 0.497, respectively). It did, however, identify factors related to immune status (nadir CD4 and CD4 change) as the most important factors for viral-associated NADC risk; and older age as the most important factor for non-viral associated NADC risk. Future studies should investigate individual NADC sites’ risk factors and utilize genetic epidemiology to understand the interplay of post-ART immune response factors with lifestyle risk factors for cancer.

Available for download on Friday, October 01, 2021

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