Date of Award
Doctor of Philosophy (PhD)
Human immunodeficiency virus type 1 (HIV-1) is the causative agent of acquired immune deficiency syndrome (AIDS), a disease responsible for extensive morbidity and mortality worldwide. Despite more than thirty years of research since the discovery of HIV-1, no cure or vaccine yet exists. HIV-1 infection, while treatable with suppressive antiretroviral therapy drugs (ART), establishes lifelong persistence in the infected host as a natural consequence of the viral life cycle and the dynamic properties of the human immune cells in which HIV-1 propagates. This persistence is driven by populations of rare, long-lived HIV-1-infected cells, termed latently infected cells (LICs), that are refractory to immune clearance and viral cytopathic effects. Interruption of suppressive therapy – even after years of continuous and effective treatment – rapidly leads to virological rebound, requiring infected persons to remain on ART indefinitely. As the need to maintain lifelong daily ART imposes a substantial compliance burden on those infected, two major goals of HIV-1 research, broadly, concern (1) developing new therapeutic modalities that may alleviate some drawbacks to ART, and (2) identifying means with which to target and eradicate LICs as an approach to curing HIV-1 infection. To these ends, in the first three chapters of my thesis, I discuss my work demonstrating the utility of highly potent anti-HIV-1 antibodies in a number of therapeutic contexts. As antibody therapy expectedly did not result in cure, I was later motivated to study the nature of LIC formation and persistence. The fourth chapter of this thesis outlines my work to develop new molecular tools to interrogate LICs in a humanized mouse model of HIV-1 infection.
Horwitz, Joshua Abraham, "Dynamics of HIV-1 Infection and Therapy In Vivo" (2016). Student Theses and Dissertations. 300.