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Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist despite suppressive antiretroviral therapy (ART). Because latent Toxoplasma infection (LTI) may adversely impact brain function, we investigated its impact on neurocognitive impairment (NCI) in people living with HIV disease. Methods. Two hundred sixty-three HIV-infected adults underwent comprehensive neurocognitive assessments and had anti-Toxoplasma gondii immunoglobulin G (anti-Toxo IgG) measured by qualitative and quantitative enzyme-linked immunosorbent assays. Results. Participants were mostly middle-aged white men who were taking ART (70%). LTI was detected in 30 (11.4%) participants and was associated with a significantly greater prevalence of global NCI (LTI positive [ LTI+]=57% and LTI negative [ LTI-]=34%) (odds ratio, 1.67; 95% confidence interval, 1.17-2.40; P=.017). Deficits were more prevalent in the LTI+ vs the LTI -group in 6 of 7 cognitive domains with statistical significance reached for delayed recall (P<.01). The probability of NCI increased with higher CD4(+) T-cell counts among LTI+ individuals but with lower CD4(+) T-cell counts in LTI-persons. A strong correlation (r=.93) between anti-Toxo IgG levels and global deficit score was found in a subgroup of 9 patients. Biomarkers indicative of central nervous system inflammation did not differ between LTI+ and LTI-participants. Conclusions. In this cross-sectional analysis, LTI was associated with NCI, especially in those with higher CD4(+) T-cell counts. Longitudinal studies to investigate the role of neuroinflammation and neuronal injury in LTI patients with NCI and trials of anti-Toxoplasma therapy should be pursued.