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Depression is prevalent among people living with HIV/AIDS (PLWHA), but there are few longitudinal studies investigating the prevalence of depression among HIV respondents in Taiwan.This study examined the trend in the prevalence of depression and its main predictors among PLWHA in Taiwan.This study analyzed the 2-million random-sample data set of the Taiwanese longitudinal health research database using data from 2000 to 2011and applied the Internal Classification of Diseases, 9th Revision, Clinical Modification diagnostic codes for the detection of HIV infection and depression. Chi-square tests and logistic regression analyses were conducted to determine predictive factors for depression.A total of 769 PLWHA who met the criterion of HIV infection were extracted from the database. Of these respondents, 20.03% had a diagnosis of depression after their HIV-positive diagnosis. The annual prevalence of depression among the study respondents increased significantly from 1.95% in 2000 to 6.93% in 2011 according to time trend analysis (χ2 = 6.428, df =11, p = .03). Multivariate, logistic regression analysis indicated a history of drug abuse was the main predictor of a diagnosis of depression.The increasing trend in the prevalence of depression revealed an urgent need for the development of care programs for PLWHA with depression. Such programs should take into consideration a history of drug abuse as a strong risk factor for the development of depression.