Systemic Inflammation before and after antiretroviral therapy initiation as a predictor of immune response among HIV infected individuals in Manitoba

Abstract

In spite of the benefits of antiretroviral therapy (ART), immune activation remains higher in HIV-positive individuals on ART than in non-infected persons.1 2 Furthermore, chronic inflammation in HIV-positive persons on ART has been linked to poor morbidity and mortality outcomes.3 Individuals with HIV are at a higher risk for end-organ diseases.4 What remains unknown is whether systemic inflammation itself is related to impaired immune recovery following commencement of ART, and as a result, adverse clinical outcomes. We intend to explore whether systemic inflammation prior to, and following the commencement of, ART is a predictor of immune response in persons with HIV in Manitoba. Using samples taken from prospectively enrolled HIV-positive individuals, whom we enrolled prior to ART initiation and followed for one year, we will compare levels of pro-inflammatory cytokines and markers of T cell activation before and after the commencement of ART. We will then correlate levels of immune activation with immune response and adverse clinical outcomes. We hypothesize that higher levels of systemic immune activation will be associated with suboptimal immune recovery on ART and adverse clinical outcomes, and that the inflammation will be higher in protease based regimens. An understanding of the factors involved in immune activation may help to improve immune recovery and ultimately lead to the development of therapeutic adjuncts to ART.