Hilldorfer IV, Benedict B.
(2013)
THE RELATIONSHIP BETWEEN RESIDUAL VIREMIA AND CHRONIC
INFLAMMATION IN PATIENTS ON LONG-TERM ANTIRETROVIRAL THERAPY.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Since the development of combination antiretroviral therapy, morbidity and
mortality due to AIDS-related malignancies has declined significantly. In most patients,
daily administration of a multidrug antiretroviral regimen is sufficient to suppress viral
replication and reduce immune activation and inflammation. In spite of this, residual
viremia persists for many years in the vast majority of patients, and immune activation
remains higher than pre-infection baseline. Chronic immune activation and inflammation
are associated with a variety of adverse health consequences including higher risks of
cancer, heart disease, liver, and kidney problems. Moreover, these risks are not
normalized to those of healthy individuals when patients are on long-term antiretroviral
therapy.
Due to the deleterious effects of chronic inflammation, it is desirable to develop
treatments aimed at reducing immune activation in patients on suppressive antiretroviral
therapy. Unfortunately, the variables that drive chronic inflammation are unclear, but
could result from multiple factors including antigenic stimulation via residual viremia,
microbial translocation from the gut into the blood due to damage of the gastrointestinal
tract, and a reduction in the ability of the immune system to mount rapid immune
responses against commonly encountered pathogens. In order to better control chronic
immune activation, the variables that influence it must first be determined.
iv
In this thesis, I report on two studies of residual viremia in the context of immune
activation. The first is a report of virologic data derived from a clinical trial of patients
with sub-optimal reconstitution of the CD4+ T cell compartment. The second is a study
regarding the relationship between immune activation, residual viremia, and CD4+ T cell
count in the context of regulatory T cells. Neither study found a correlation between
immune activation and residual viremia, indicating that immune activation may not be
not driven by continuous antigenic stimulation provided by persistent virion production.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
26 August 2013 |
| Date Type: |
Publication |
| Defense Date: |
August 2013 |
| Approval Date: |
26 August 2013 |
| Submission Date: |
26 August 2013 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
48 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Virology and Microbiology |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
HIV, residual viremia, inflammation, immune activation |
| Date Deposited: |
26 Aug 2013 18:59 |
| Last Modified: |
15 Nov 2016 14:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/19727 |
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