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This study examined prospectively the effects of stressful events, depressive symptoms, social support, coping methods, and cortisol levels on progression of HIV-1 infection.Eighty-two homosexual men with HIV type-1 infection without AIDS or symptoms at baseline were studied every 6 months for up to 7.5 years. Men were recruited from rural and urban areas in North Carolina, and none was using anti-retroviral medications at entry. Disease progression was defined as CD4+ lymphocyte count <200/μl or the presence of an AIDS indicator condition.Cox regression models with time-dependent covariates were used adjusting for race, baseline CD4+ count and viral load, and cumulative average antiretroviral medications. Faster progression to AIDS was associated with higher cumulative average stressful life events, coping by means of denial, and higher serum cortisol as well as with lower cumulative average satisfaction with social support. Other background (e.g., age, education) and health habit variables (e.g., tobacco use, risky sexual behavior) did not significantly predict disease progression. The risk of AIDS was approximately doubled for every 1.5-unit decrease in cumulative average support satisfaction and for every cumulative average increase of one severe stressor, one unit of denial, and 5 μg/dl of cortisol.Further research is needed to determine if treatments based on these findings might alter the clinical course of HIV-1 infection.