This proposed 5 year project, which will examine acute stress responses in a total of 120 (of 144 recruited) HIV-infected symptomatic but not AIDS- defined men and women, is subdivided into three separate projects 4A-C. In our previous NIMH-funding studies, we have examined the impact of the CBSM intervention on immune reconstitution. To date, our findings are consistent with the contention that the CBSM intervention acts to modulate coping and normalize measures of immunologic status in asymptomatic HIV infected individuals. While the CBSM has been shown to decrease EBV antibody titers in asymptomatic HIV infected individuals. While the CBSM has been shown to decrease EBV antibody titers in asymptomatic HIV infected individuals, this finding was not replicated in symptomatic HIV infected individuals, although the symptomatic subjects did not display immunologic normalization of HSV-2 antibody titers following CBSM intervention. Because stressors and other psychosocial factors have been shown to impair certain aspects of cell-mediated immunity, and because interventions, such as CBSM, have been demonstrated to normalize some stress associated immunologic functional impairments, we propose in projects A and B to examine the impact of the CBSM intervention on resting immune functioning (CD4 and NK cell count, NK cytotoxicity, lymphoproliferative response to PHA) and surveillance of herpes viruses (EBV, HHV-6, HSV-2) in symptomatic HIV infected men and women on combination antiretroviral therapy compared with control subjects. In addition, projects A and B extend our previous NIMH-funded studies of acute stress responses in HIV seropositive men and women by moving the focus of the investigation from the laboratory manipulation to using the laboratory manipulation as a tool toward the examination of the effectiveness of the cognitive behavioral stress management (CBSM) intervention in enhancing immuno-cellular functioning. Two types of acute challenge, a psychological stressor (evaluate speech stress) and a physical stressor (bicycle exercise) will be used to probe for the impact, before and after the CBSM intervention on the autonomic (blood pressure, cardiac contractility indices, respiratory sinus arrhythmia), neuroendocrine plasma catecholamines, ACTH, cortisol), and immuno-cellular (lymphocytes with phenotypes, lymphocyte activation and adhesion markers, NK number with intracellular perforin assessment and NK cytotoxicity, and lymphocytic proliferation in response to mitogen) stress responses in the HIV symptomatic gay men enrolled in 0002 and the HIV symptomatic women enrolled in 0004. Equal numbers of subjects will either received CBSM plus standard-care treatment or a control procedure in which subjects will receive standard-care only. In previous research, we observed that HIV infected a symptomatic and symptomatic subjects displayed attenuated increased in NK cytotoxicity relative to seronegative subjects during speech stress. Thus in project C using in vitro methodology, we will examine in the 60 (of 72 recruited) men and women participating in projects A and B. 1) the influence of catecholamines cortisol and the type 1 cytokines, IFN-gamma and IL-2 on the NK cytotoxicity observed during speech: and 2) whether the impact of the CBSM intervention has a differential effect on these potential influences of NK cytotoxicity response during the psychologically stressful challenge.
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