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Background: Seizures are associated with neurological manifestations of HIV. They may be the presenting symptom and can occur at any disease stage. Aim: To determine the frequency and clinical aspects of new-onset seizures in patients with human immunodeficiency virus (HIV) infection. Methods: A study of an HIV-infected patient cohort on highly active anti-retroviral therapy (HAART) in the out-patients clinic of the Lagos state university teaching hospital, Nigeria. In a cross-sectional design, 308 HIV infected patients were recruited over a period of 1 year. Cases with a first seizure during this period were further examined. Details of demographic data, the first seizure date, seizure characteristics, neurologic complications and CD4 count at the time of the seizure were documented. Results: A total of 20 (6.5%) had new-onset seizures during the study period. 6/20 (30%) were males and 14/20 (70%), females. Their ages ranged between 22 - 51 years with a mean of 34.2 ± 8.7 years. The seizure was focal in 2/20 (10%) of cases and generalised in 90% (18/20) of cases. A total of 13/20 (65%) had recurrence of their seizures. None of the cases had focal neurological deficit at the time of the first seizure. The mean CD4 count was 165.3 ± 145.7. The mean duration on HAART was 19.5 ± 12.7 months. Cases with CD4 counts ≤200 cells/mm3 constituted 70% (14/20) whilst those with CD4 counts >200 made up 30% (6/20) [p = 0.666]. Conclusions: Seizures remain a significant neurological manifestation of HIV infection and has a high recurrence rate. It occurs more commonly in the advanced stage with severe immune suppression and may be attributable to HIV encephalopathy. Early treatment would reduce the burden and improve patient’s quality of life.