Grant: Operating Grant - PA: HIV/AIDS Bridge Funding - Biomedical/Clinical Stream

With effective antiretroviral therapy preventing the progression of human immunodeficiency virus (HIV) infection to the acquired immune deficiency syndrome (AIDS) HIV-infected individuals are living longer but continue to suffer more morbidity and mortality than the general population. Various factors may contribute to elevated morbidity and mortality including long term effects of HIV infection itself, long term exposure to antiretroviral drugs and co-infection with other pathogens. Cytomegalovirus (CMV) is a common virus infecting more than 80% of human immunodeficiency virus (HIV)-infected individuals. Infection with CMV is generally a clinical problem only in newborns and people with weakened immune systems. In the old elderly (people > 80 years), the immune response against CMV grows to unusually high levels, which changes how the immune system looks and acts. These changes produce an "Immune Risk Profile" (IRP), which is associated with mortality, frailty, physical signs of immune system aging, diabetes, mental decline and other age-related morbidities. In HIV-infected individuals, the immune response against CMV grows to levels associated with these age-related morbidities at much younger ages. In this and other ways, HIV-infected individuals appear to undergo accelerated aging, which makes them susceptible to age-related co-morbidities earlier in life. We and others have shown that the size of the immune response against CMV in HIV-infected individuals affects immune system recovery. The aim of this research is to address potential causes of the unusually large expansion of the CMV immune response in HIV infection. Different treatments, some already available and others under development would be indicated by the results.