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As the lives of people living with HIV (PLWH) become increasingly normalized, more focus is being given to the associated comorbidities of HIV, including those related to mental health such as depression. This study aims to evaluate the correlation between depressive symptoms and HIV outcomes in Vietnam through the measurement of CD4 cell count. A mixed design was utilized, in which both a longitudinal assessment of CD4 cell counts and a cross-sectional survey of depressive symptoms were conducted on 481 patients in the Bach Mai and Ha Dong HIV clinics (Hanoi, Vietnam). CD4 cell count data was extracted from the medical records of participants, and depressive symptoms were screened using the Patient Health Questionnaire (PHQ-9). The results illustrate that the presence of moderately severe to severe depressive symptoms is associated with lower CD4 cell counts, indicating poorer HIV outcomes resulting from comorbid depression. This correlation was especially noticeable in the PHQ-9 items for psychomotor agitation/retardation (p < 0.05) and suicidal ideation (p < 0.05). Future policy and treatment options for HIV in Vietnam should consider the presence of comorbid mental health conditions in order to provide more suitable and effective treatment in the goal of providing a higher quality of life for PLWH. [ABSTRACT FROM AUTHOR]