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An important issue is how depression and substance use interact with the control of the HIV treatment continuum. A group of 14,380 persons with HIV were studied to determine how depressive symptoms along with alcohol and other substance use affect the continuum of care in these patients. Standard statistical procedures were used in the analysis. In those with no or mild depressive symptoms, heavy alcohol had no association with viral suppression; but, among those with moderate or severe symptoms heavy alcohol use did have a negative effect on viral load. However, the investigators did not find an effect with retention in care or ART prescription use. Also, they did not find a relationship with other substance use. The findings emphasize the negative effect of moderate or severe depression, especially those with heavy alcohol ingestion. Both aspects of care require diligent medical attention.