Date of Award
Doctor of Philosophy (PhD)
Michael R. Betts
Every year, HIV-positive adolescents add to the growing number of HIV-infected individuals. In fact, as of 2005, 50% of newly diagnosed persons with HIV worldwide were youth with an estimated 10.3 million between the ages of 15 and 24. Adolescents will live with HIV 20 years longer than their adult counterparts, but disease progression in them is less understood. It is well known that immune activation is prognostic of chronic disease progression in adults and is often reduced when subjects go on therapy. It is unclear whether immune activation is entirely eliminated in adolescents on therapy. To date, studies of HIV-positive adolescents have been limited by design and methodology, resulting in a lack of research addressing the relationship between outcome of antiretroviral therapy in adolescents and immune activation. To this end, we designed a study to examine the relationship between therapeutic outcomes and immune activation in HIV-positive adolescents. We assembled a cohort of 35 HIV-infected and 12 healthy adolescents and measured immune activation (CD38,CD38/HLA-DR, Ki67) in both baseline and longitudinal data. As expected, cell turnover was greatly increased in memory CD4 T cells over time. We found that levels of immune activation in both CD8 and CD4 T cell subsets was elevated in viremic subjects at baseline and after long-term therapy. One clear distinguishing factor of pathogenic HIV-infection is increased microbial translocation, which can be measured by CD14 release by activated monocytes. We report sustained elevation of sCD14 in viremic adolescents, which directly correlated to immune activation. Our results show that adolescents who are not therapy compliant have elevated immune activation and turnover. Collectively, our results show that in the presence of suboptimal therapy measures associated with disease progression are elevated. Therefore, it is necessary to reconsider current treatment guidelines in adolescents to promote optimal adherence and virologic control in this growing population of HIV-infected individuals.
Haney, Danielle, "Impact of HAART on T Cell activation in HIV-Infected Adolescents" (2012). Publicly Accessible Penn Dissertations. 517.