Treatment to reduce inflammation and improve immune recovery among older HIV pts

Hennepin Healthcare Research Institute, Minneapolis MN

Investigators

Linked publications & trials

Abstract

DESCRIPTION: Treated HIV positive patients are at increased risk for cardiovascular disease (CVD), cancer, and other HIV- associated non-AIDS conditions. Ongoing immune activation, despite effective treatment with antiretroviral therapy (ART), increases risk for CVD and non-AIDS conditions, but also contributes to lymphatic tissue fibrosis, limiting immune recovery that further increases risk for non-AIDS conditions. Biologic aging also leads to systemic inflammation and waning immune function, and, thus, non-AIDS conditions and poly-morbidity will continue to increase as the HIV population ages. Identifying safe treatments that target this pathology represents a major unmet need for older HIV positive patients. We propose a randomized placebo-controlled trial of losartan (100mg daily) among n=120 antiretroviral-treated HIV positive persons age >50 years receiving effective ART with undetectable HIV RNA levels. We will study the treatment effects of losartan on changes in IL-6 levels over 6 months and changes in peripheral blood CD4 count over 12 months. We hypothesize that losartan treatment will: a) reduce systemic inflammation that will be accounted for through reductions in monocyte activation within peripheral blood, and b) lead to immune recovery, as reflected in blood CD4+ count, via down-regulating immune activation and TGF-?-mediated fibrosis in lymphatic tissues that will improve T- cell homeostasis and survival of naive T-cells. Our investigative team has helped define the role of inflammation in non-AIDS disease risk as well as developed the model that links lymph node fibrosis with impaired T-cell homeostasis. This work directly informed our choice of outcomes, which both test fundamental HIV pathogenesis questions and will determine if losartan improves immune activation and immune recovery to a degree that may be clinically relevant. Our methods and hypotheses are innovative, our intervention is novel in the context of HIV infection, and our approach provides essential randomized data to inform and justify the expense of subsequent clinical outcome trials. In summary, this translational trial addresses a high priority HIV research agenda to identify disease-modifying strategies for non-AIDS conditions among older patients.