Simian AIDS: Social stress, endocrine &immune function

University Of California Davis, Davis CA

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): In the past decade, a growing body of evidence has accumulated showing that social stressors, bereavement, and the absence of social support experienced during the asymptomatic stage of HIV disease are associated with indicators of more rapid disease progression. Both in vivo and in vitro studies have suggested that the mechanisms mediating these effects involve the two major stress response systems, the sympathetic-adreno-medullary (SAM), and the hypothalamic-pituitary-adrenocortical (HPA). These results suggest that potentially useful adjunct therapies -behavioral or pharmacological- for HIV-infected individuals that target these physiological systems might lead to a reduction in HIV viral load (and longer survival) by altering stress-hormone concentrations, receptor numbers on immune cells, and cellular immune responses that are important in regulating viral expression. Previous research using the SIV/rhesus macaque model of AIDS has demonstrated experimentally that psychosocial factors can affect the establishment of viral set-point and survival. The goal of the proposed study is to determine the therapeutic efficacy of social manipulations and pharmacological substances that are aimed at reducing SAM and HPA activity, enhancing immune function, and lowering viral load once a stable set-point has been established. A number of viral, endocrine, functional immune, and histological measures will be obtained at regular intervals to test the hypotheses that interventions targeting these physiological systems can affect SIV disease progression, and that the beneficial effects are mediated through stress response system effects on cell-mediated immunity. Our specific aims are to determine whether social stress and social stability affect SIV disease progression following establishment of viral set-point, and to generate pilot data on whether nadolol, a beta-adrenergic receptor antagonist, and DHEA, an adrenal androgen associated with enhanced immune function, can ameliorate the effects of a social stressor on viral set-point and measures of SIV disease progression. This research will provide important new information on the interrelations of stress-response systems and immune function in the context of immunodeficiency disease, and will provide data demonstrating the efficacy of adjunct treatments that reduce the harmful physiological consequences of stress in AIDS.