Background:  Whether brain injury and cognitive impairment persist in the setting of HAART and stable disease remains to be determined. The HIV Neuroimaging Consortium, comprised of 7 US sites, was formed to prospectively examine the effects of HIV on brain function and identify biomarkers of risk and progression using a combined imaging approach, including morphometry and magnetic resonance spectroscopy (MRS), in a cohort of 300 HIV-infected patients with advanced and chronic disease on HAART.

Methods:  MRS analyses were based on 263 patients classified into 4 groups:  HIV^– controls (n = 28), HIV⁺ neuro-asymptomatic (n = 122), ADC stage 0.5 (n = 64), and ADC stage 1 to 3 (n = 49). Mean age was 47, mean duration of infection, 12.1 years, detectable plasma RNA level in 24%, log₁₀, current CD4 count mean = 2.4, log₁₀ nadir CD4 count mean = 1.5, 84% on HAART for a mean of 4 years. MRS metabolite ratios included:  N-acetyl aspartate (NAA)/creatinine (Cr), choline (Cho)/Cr, and myoinositol/Cr in the basal ganglia, frontal white matter, and mid-frontal cortex. Group comparisons were based on ANOVA and predictors of brain injury were identified in linear regression models using Akaike Information Criterion.

Results:  Primary analyses revealed significant differences between controls and HIV subjects for the neuro-asymptomatic and ADC groups in the myoinositol/Cr in the frontal white matter (p <0.001), the basal ganglia (p = 0.001), and mid-frontal cortex (p = 0.001), and the Cho/Cr in the basal ganglia (p = 0.007) and mid-frontal cortex (p = 0.003). Secondary analysis revealed lower NAA/Cr in basal ganglia in ADC stages 1 to 3 compared to the neuro-asympptomatic group (p = 0.003). Duration of infection, detectable plasma RNA and ADC, but not the absence of central nervous system penetrating agents were significantly associated with brain injury measured by MRS. Factor analysis identified 4 metabolic patterns:  basal ganglia, neuronal, and 2 inflammatory factors, Cho/Cr in the frontal white matter, mid-frontal cortex, and the other, myoinositol/Cr in all 3 regions. Logistic regression identified only the basal ganglia factor as a significant predictor of ADC.

Conclusions:  After 15 years of HAART, HIV patients continue to show patterns of central nervous system injury in the setting of chronic and stable disease. Although the impact is primarily subcortical, expansion to the cortex is now evident. Importantly, HIV neuro-asymptomatic subjects now show diffuse inflammatory changes, whereas ADC subjects also show neuronal injury primarily in the basal ganglia, consistent with a 2-stage model of brain injury. Longitudinal studies are underway to assess the significance of these findings.