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.
","abstract_html":"<p>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.</p>","abstract_has_math":false,"creators":["Horwitz, Joshua Abraham"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Michel C. Nussenzweig"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-01-01T08:00:00Z","date_published":"2016-01-01T08:00:00Z","updated_at":"2026-07-24T04:10:53Z","subjects":["HIV-1","latency","antiretroviral therapy","LICs","antibody therapy","molecular tools","Life Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/300","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Michel C. Nussenzweig"]},{"key":"dc:creator","label":"Author","values":["Horwitz, Joshua Abraham"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["HIV-1","latency","antiretroviral therapy","LICs","antibody therapy","molecular tools","Life Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/300"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Dynamics of HIV-1 Infection and Therapy In Vivo"]}]}],"canonical_facts":{"dc:contributor":["Michel C. Nussenzweig"],"dc:creator":["Horwitz, Joshua Abraham"],"dc:description.abstract":["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.
"],"dc:identifier":["https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/300"],"dc:subject":["HIV-1","latency","antiretroviral therapy","LICs","antibody therapy","molecular tools","Life Sciences"],"dc:title":["Dynamics of HIV-1 Infection and Therapy In Vivo"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T04:10:53Z"}