Project Summary/Abstract
Infection with Human Immunodeficiency Virus (HIV) affects an estimated 36.7 million worldwide. In the United
States, an estimated 1.1 million people are infected. As the access to antiretroviral treatment (ART) has
increased, the population of people infected with HIV live longer. Patients with viral suppression have
increased life expectancy. However, compare to age-matched individual without HIV infection, they have
shortened lifespan with higher rates of comorbidities, including cardiovascular diseases (CVD). Persistent
inflammation and chronic immune activation caused by HIV and likely ART results in a pro-inflammatory state
that increases the risk for cardiovascular disease. Though statins have been used to decrease the effects of
hyperlipidemia and inflammation on progression of cardiovascular disease, use of statins is underutilized in
patients with HIV and falls short of realistic goals for LDL reduction in these high-risk patients. Human CD24Fc,
developed by OncoImmune, Inc., is a recombinant fusion protein composed of the extracellular domain of
human CD24 and the Fc fragment of human IgG1. CD24 is expressed in wide range of cell types as an
important genetic modifier for several autoimmune diseases and inflammation in response to danger-
associated molecular pattern (DAMPs). Our published data demonstrated that CD24Fc prevented SIV-infected
macaques from developing AIDS through induction of inhibitors of inflammation while suppressing promotors
for inflammation and autoimmune disease. Our unpublished data showed that in human CD34+ hematopoietic
stem cell-reconstituted mouse HIV model, CD24Fc treatment suppressed production of inflammatory cytokines
and reduced activation and loss of CD4 T cells. In a Phase I clinical trial in healthy people, ascending doses of
CD24Fc (up to 240 mg) significantly decreased fasting LDL level and induced leptin level in serum. The
reduction of fasting LDL by CD24Fc is confirmed in a Phase IIa clinical trial in patients undergo hematopoietic
stem cell transplantation for leukemia. The results are consistent with the recently discovered connection
between inflammation and metabolic disorders. Based on these preliminary results, we propose that
treatment with CD24Fc can fortify negative regulation of innate immune responses, decrease LDL, and
thus reduce the risk of cardiovascular disease in HIV patients. To test this hypothesis, we will evaluate, in
HIV-infected individuals, the safety and efficacy of CD24Fc in normalizing lipid metabolism, reducing T cell
activation and viral reservoir. Sixty-four patients aged over 50 with HIV infection who are virally suppressed on
antiretroviral therapy for over 2 years will be randomized in a 1:1 ratio to receive either 240mg of CD24Fc or
placebo for 12 weeks, with a 24-week follow-up period. We will evaluate the safety and tolerability of the drug
as well as the changes in LDL and other cellular and soluble inflammatory parameters with CD24Fc treatment
and perform nuclear imaging studies to evaluate changes in myocardial perfusion and function with CD24Fc
treatment. This clinical trial will enroll an HIV cohort with 78% of African American. The study will uncover
critical knowledge in our understanding of the pathogenesis of adverse cardiovascular outcomes in HIV-
infected patients and test a novel approach for treating refractory hyperlipidemia.
