Background:  While combination ART (cART) has prolonged survival in HIV⁺ patients, a high prevalence of neurocognitive impairment (NCI) has persisted and cART-related metabolic syndrome has emerged as a complication. We studied the relationship of NCI and metabolic syndrome in HIV-infected participants in CHARTER, an observational study at academic clinics in the 6 US cities.

Methods:  In a cross-sectional substudy, 145 HIV-infected participants were selected from 1534 enrolled in CHARTER based on their provision of a fasting blood sample. NCI was defined as global deficit score ≥0.5 based on a battery of neuropsychological tests that adjust for age-, education-, and race-specific norms and are validated to detect HIV-related impairment. Effects on NCI of demographics (age, gender, education, race/ethnicity), biomarkers of HIV disease (current and nadir CD4 count, plasma HIV levels, and AIDS diagnosis), antiretroviral (ARV) history, and metabolic syndrome-related variables (clinical history of type II diabetes), body mass index, waist circumference, blood pressure, glucose, insulin, insulin resistance, triglycerides, high- and low-density lipoproteins cholesterol (LDL-C), and serum leptin were tested in uni- and multi-variate models.

Results:  Substudy participants were mostly white (58%) and male (86%) and averaged 46 years old. Prevalence of NCI was 53 of 145 (37%), consistent with other estimates in the HAART era. In univariate models, the only demographic variable that correlated with NCI was less education (12.6 vs 13.4 years, p <0.05). Of the metabolic syndrome-related variables, correlates of NCI included greater waist circumference (98 vs 90 cm, p <0.05), lower LDL-C (89 vs 106 mg/dL, p <0.01), and higher prevalence of type II diabetes (16 vs 2%, p <0.01). In multivariate logistic regression analysis (n = 84), waist circumference (OR = 1.06/cm), type II diabetes (OR = 13), and AIDS (OR = 89), but not LDL-C or other metabolic factors, were significantly increased in those with NCI (p <0.01 for all 3).

Conclusions:  Of components of the metabolic syndrome, only waist size and diabetes correlated with higher risk of NCI. Insulin resistance, a strong correlate of diabetes type II, was not increased in NCI. Diabetes, but not waist size, has been previously correlated with cognitive impairment in HIV-infected populations, but the mechanism(s) are unclear. Weight reduction and ARV drugs that are less likely to induce metabolic syndrome and diabetes might help to protect the brain.