Pilot Award Recipient: Marc O. Siegel, MD

The Impact of HCV on Aging Through Immune Activation in HIV Infected Subjects
September 15, 2014

As the average age of the US HIV infected population has risen in the last 3 decades there is increasing concern regarding the accelerated aging that has been documented. HIV infected subjects suffer from much higher rates of noninfectious comorbidities than their age matched uninfected peers. Understanding the mechanism for this aging will allow clinicians to intervene in this process and reduce their associated mobidity and mortality.

The purpose of this pilot study is to obtain preliminary data from different groups of subjects in order to examine the influence of HCV infection on serum and cellular markers of immune activation in HCV/HIV co-infected patients. These results will be correlated with aging by assessing telomere length as a biomarker for biological aging in vivo. We hypothesize that coinfection with HCV accelerates the rate of aging in HIV infected subjects by exaggerating the level of immune activation. The study will consist of 4 groups of age-matched subjects. Group 1 will include 15 HCV/HIV uninfected subjects who will be our control group. Group 2 will include 15 HIV infected subjects who are suppressed on antiretroviral therapy, Group 3 will include 15 noncirrhotic subjects with untreated chronic hepatitis C, and Group 4 will include 15 noncirrhotic HCV/HIV coinfected subjects who are suppressed on antiretroviral therapy but naïve to HCV therapy.

All of the subjects in each group will have serum inflammatory cytokines associated with the immune activation analyzed including sCD14, sCD163, IL-6, D-dimer, TNF-α, hsCRP, and IP-10. In addition, cellular markers of immune activation will be investigated by measuring the proportion of CD4+ and CD8+ T cells coexpressing HLA-DR, CD69 and CD38. Finally, premature aging will be assessed by measuring telomere length and these results will be correlated to the levels of immune activation that was identified. The elevated markers of immune activation that are identified as being correlated with accelerated aging from this preliminary study will be looked at in a more extensive prospective study. We will plan on examining the effects of either statin therapy or HIV integrase therapy, both of which have been shown to decrease markers of immune activation, on the levels of these cytokines.