Major depressive disorder (MDD) increases further morbidity and mortality of patients with retroviral disease (RVD) or human immunodeficiency virus (HIV) infection. This study aimed to determine the prevalence of MDD and its contributing factors among them. Depressive symptoms were screened using the Hospital Anxiety Depression Scale (HADS), and MDD was diagnosed with the Mini International Neuropsychiatric Interview (MINI). Of the total 210 RVD patients, 27(12.9%) had MDD. The contributing factors for MDD include amphetamine-type stimulants use, social support system, and CD4 count. Interventions for RVD patients should include counselling for those abusing drugs, increasing support system and adherence to treatment.