To describe patterns of depressive symptoms across 10-years by HIV status and to determine the associations between depressive symptom patterns, HIV status, and clinical profiles of persons living with HIV from the Multicenter AIDS Cohort Study (N = 980) and Women's Interagency HIV Study (N = 1744). Group-based trajectory models were used to identify depressive symptoms patterns between 2004 and 2013. Multinomial logistic regressions were conducted to determine associations of depression risk patterns. A 3-group model emerged among HIV-negative women (low: 58%; moderate: 31%; severe: 11%); 5-groups emerged among HIV-positive women (low: 28%; moderate: 31%; high: 25%; decreased: 7%; severe: 9%). A 4-group model emerged among HIV-negative (low: 52%; moderate: 15%; high: 23%; severe: 10%) and HIV-positive men (low: 34%; moderate: 34%; high: 22%; severe: 10%). HIV+ women had higher odds for moderate (adjusted odds ratio [AOR] 2.10, 95% CI 1.63-2.70) and severe (AOR 1.96, 95% CI 1.33-2.91) depression risk groups, compared to low depression risk. HIV+ men had higher odds for moderate depression risk (AOR 3.23, 95% CI 2.22-4.69), compared to low risk. The Framingham Risk Score, ART use, and unsuppressed viral load were associated with depressive symptom patterns. Clinicians should consider the impact that depressive symptoms may have on HIV prognosis and clinical indicators of comorbid illnesses.