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The objective of this study was to test the association of positive affect as measured by the Center for Epidemiologic Studies Depression Scale (CES-D) with risk of AIDS mortality, controlling for the other CES-D subscales and laboratory measures of disease progression.Data come from the San Francisco Men's Health Study, a prospective study of a household probability sample of single men in San Francisco. The subjects were 407 men who were HIV+ at study baseline.In time-dependent Cox proportional hazards models, the positive affect subscale of the CES-D was significantly associated with lower risk of AIDS mortality (RR = 0.89, CI = 0.84-0.95). When risk estimates were adjusted for time-dependent covariates of CD4, serum β2-microglobulin, P24 antigen, antiretroviral use, and the other subscales of the CES-D, positive affect remained significantly predictive of lower risk of AIDS mortality (RR = 0.90, CI = 0.85-0.97). When the CES-D subscale predictors were lagged by 12, 24, and 36 months in order to address the possibility that positive affect was simply a marker for better health, positive affect remained significantly predictive lagged by 12 months and marginally predictive lagged by 24 months.Positive affect seems to be the “active ingredient” in the association of scores on the CES-D depressive mood scale and mortality in this sample of HIV+ men. Future work should expand the traditional negative-affect-only focus to encompass the significant role that positive affect plays in living with HIV.