To prove that primitive reflexes are independent markers of symptomatic human immunodeficiency virus type-1 (HIV-1) infection, a case-control study was carried out in a tertiary care, university teaching hospital. Thirty HIV-1-positive symptomatic cases, 30 seropositive asymptomatic controls and 30 HIV-1 seronegative controls consented to participate and were selected consecutively. A single examiner blinded to serostatus administered the Mini-Mental State Exam and a structured neurological exam to each participant. Up to 45% of cases had cognitive impairment. The occurrence of neurologic signs between seropositive cases and seropositive controls was similar, but the number of primitive reflexes was significantly higher in cases (P < 0.001). By multivariate discriminant analysis, all primitive reflexes but two correctly classified 83.3% of all participants (P = 0.0013). The model had a positive predictive value of 97% when motor, mood, and cognitive symptoms were added (P = 0.0001). Primitive reflexes were independent predictors of HIV-1 serostatus, especially for those with cognitive dysfunction. Primitive reflexes should be included in future case definitions of HIV-1-related neurocognitive disorders.