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HIV can damage neurons leading to cognitive impairment. Epidemiological observations suggest that neuropsychological impairment might progress despite successful HAART therapy, but available prevalence estimates are based on populations that were selected for impairment.Of 433 advanced AIDS patients with documented immune reconstitution (CD4 lymphocyte counts < 50 before and > 100 cells/μl after HAART), 286 had brief assessments of cognition (Trailmaking A/B and Digit Symbol Tests) at least once, no confounding neurological conditions, and available neuropsychological norms with comprehensive demographic corrections. At entry, most were immune reconstituted on HAART (median CD4 cell count 230 cells/μl) and HIV was suppressed (65% < 500; only 14% > 20 000 RNA copies/ml).Over one quarter (27%) of participants exhibited impairment at their initial neuropsychological assessment, a rate nearly twice that expected in a normal (HIV-uninfected) reference population (14%). These impaired participants did not differ from the unimpaired group with respect to age, sex, education, race, CD4 lymphocyte counts, or HIV-RNA levels. Improved performance on neuropsychological tests was documented over a 2-year period 3–5 years after initiating HAART. This improvement was marginally associated with the continued or improving control of plasma HIV-RNA levels, but not with concurrent levels of immune recovery (CD4 lymphocyte counts).Most advanced AIDS patients responding to HAART for prolonged periods have stable or improving cognition, but remain more likely to be impaired than the general population. During HAART, improving test performance probably reflects both practice effects and continuing neurological recovery after more than 3 years of HAART.