Latent Toxoplasma Infection and Higher Toxoplasma gondii Immunoglobulin G Levels Are Associated With Worse Neurocognitive Functioning in HIV-Infected Adults

Abstract

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.

Keywords: Anti–Toxoplasma gondii IgG; HIV-1 infection; latent Toxoplasma infection; latent toxoplasmosis; neurocognitive impairment.

Figure 1.

Global and domain impairment by latent Toxoplasma infection (LTI) status. Deficits were more prevalent in the LTI-positive (LTI⁺) vs the LTI-negative (LTI^–) group in 6 of 7 cognitive domains, and these differences reach statistical significance for global impairment and delayed recall. Abbreviation: OR, odds ratio.

Figure 2.

Logistic regression model of the probability of neurocognitive impairment (NCI) by latent Toxoplasma infection (LTI) status and CD4⁺ T-cell counts. While risk of NCI decreases with higher CD4⁺ T-cell counts in LTI-negative (LTI^–) persons (blue crosses), the opposite effect is found in LTI-positive (LTI⁺) persons (red dots). At CD4⁺ T-cell counts near 200 cells/µL, the levels of risk converge.

Figure 3.

CD4 counts and global deficit scores correlate with anti-Toxoplasma gondii immunoglobulin G (IgG) levels. A, Higher anti-Toxoplasma IgG levels correlated with higher CD4⁺ T-cell counts. B, Anti-Toxoplasma IgG levels were highly correlated with global deficit score.

Figure 4.

Effect of trimethoprim-sulfamethoxazole (TMP-SMX) treatment on neurocognitive performance. Latent Toxoplasma infection–positive participants who reported TMP-SMX use (n = 3) performed substantially better than nonusers (n = 17), but the power of this comparison was low due to small numbers of participants. Heights of bars are means; lines are standard errors.