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Abstract

The introduction and widespread use of antiretroviral therapy against Human Immunodefi-ciency Virus (HIV) has had a remarkable effect on disease progression and the longevity of infected individuals. However, the establishment of a latent viral reservoir and the inability of antiretroviral compounds to purge it has resulted in HIV infection becoming a chronic disease with a high preva-lence of comorbidities, adding significant strain to the healthcare systems as well as the affected pa-tients. Human genetic variation has previously been shown to influence HIV pathogenesis as well as the risk of developing multiple common diseases in the general population. However, the influence of genetic variation on HIV positive individuals under suppressive antiretroviral therapy remains largely unknown. This thesis examines the role of human genetic variation in determining the size and long-term dy-namics of the viral reservoir, genetic risk factors for developing HIV-related non-Hodgkin lymphoma (NHL), and how genetic risk scores (GRS) can improve the prediction of chronic kidney disease (CKD) in HIV-infected individuals. Taken together, these studies delineate the role of human genetic variation in phenotypic outcomes that are highly relevant in the era of suppressive antiretroviral treatment, while also suggesting that newly developed genetic risk scores will be capable of enhancing the pre-dictive power of current clinical risk scores.

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