To determined if there is cognitive decline in HIV subjects with CD4 ≥ 200 cells/mm3 and those with CD4 < 200 cell/mm3 , correlating CD4 counts with cognitive decline, determine the cognitive domain affected, and if detection of cognitive decline in subjects depend on the neuropsychological battery used. DESIGN: A case-control study SETTING: University of Benin Teaching Hospital, Benin City. SUBJECT:Two hundred and eighty eight (288) subjects were recruited of which 96 were subjects with CD4 ≥ 200 cells/mm3 ,96 were subject with CD4 < 200 cell/mm3 , and 96 were controls. They were stratified into groups and randomly selected from COPD, the ward, the antenatal clinic and among UBTH staff. They were matched for age, sex and education. OUTCOME MEASURES 1. Cognitive test scores as assessed by: a Community screening instrument for dementia (CSI’D); b. computerized neuropsychological test ‘Fepsy’. 2. CD4 counts. RESULT: Subjects with CD4 ≥ 200 cells/mm3 had a mean CD4 count of 266.8-± 44.323 cells/mm3 while subjects with CD4 < 200 cells/mm3 had a mean CD4 count of 118.3 ± 40.969 cells/mm3 . The mean CSI’D score for control is 66.45 ± 1.788, while the mean CSI’D score for subjects with CD4 ≥ 200 cells/mm3 is 66.313 ± 2.157 (P > 0.05). The mean CSI’D score for subjects with CD4 < 200 cells/mm3 is 56.615 ± 4.234 (P < 0.001). 32.6 of subjects with CD4 ≥ 200 cells/mm3 had abnormal cognitive function, while 99% of subjects with CD4 < 200 cells/mm3 had abnormal cognitive function, using the CSI’D score of the normal controls (i.e. normal ± 2SD) as the cut –off score. The mean scores of subjects with CD4 < 200 cells/mm3 , in all the five fepsy test items are worse (P < 0.001) compared to controls and subjects with CD4 ≥ 200 cells/mm3 . A higher percentage of subjects with CD4 < 200 cells/mm3 had abnormal cognitive function compared with subjects with CD4 ≥ 200 cells/mm3 across all five fepsy items using means score of normal as cut-off. The fepsy scores of subjects with CD4 ≥ 200 cells/mm3 is statistically insignificant compared to controls in 2 test items (Simple reaction time – both auditory and visual, Tapping task) but poorer scores were obtained in 3 test items (Binary choice and sensitivity, CVST, memory recognition). The result shows that subjects with CD4 200 – 499 cell/mm3 had a higher percentage cognitive function abnormality compared to subjects CD4 ≥ 500 cells/mm3 CONCLUSION 1. Subjects with CD4 < 200 cells/mm3 have more severe cognitive decline. 2. Subjects with CD4 ≥ 200 cells/mm3 have subtle cognitive decline, which was detected by timed task incorporated in fepsy. 3. Worsening cognitive decline correlates with falling CD4 count, as a higher percentage of subjects with CD4 < 200 cells/mm3 had abnormal cognitive function compared to subjects with CD4 ≥ 200 cells/mm3 across all the test items. 4. Memory loss, slowing of psychomotor speed and thought processes are the main cognitive domains affected at CD4 ≥ 200 cells/mm3 , but with declining CD4 < 200 cells/mm3 other cognitive domains are involved