Combination antiretroviral therapy (cART) has shifted HIV from a fatal illness to a chronic condition. However, HIV-associated neurocognitive disorder is still prevalent. The cause of this brain dysfunction remains unclear because results from cross-sectional studies are unable to determine whether there is ongoing brain injury despite cART, or brain injury prior to cART initiation. To explore this issue, we longitudinally assessed regionally specific brain volumes in treated HIV+ patients with well-controlled infections, and demographically-matched HIV- controls.
46 HIV+ and 31 HIV- completed two neuroimaging and neuropsychological testing sessions approximately 2 years apart. The neuropsychological battery covered 6 cognitive domains with 8 standard tests. A standardized z-score for each test was derived using appropriate demographic norms. A neuropsychological summary score (NPZ8) was created by averaging z-scores across the 8 tests. Tensor-based morphometry (TBM) estimated brain volumes at both visits, and change in brain volume over time. General linear models assessed the correlation of HIV status, and current and nadir CD4 with brain volumes, change in brain volume, NPZ8 and change in NPZ8.
The two groups were demographically similar (HIV+ age [mean±SD]: 47±13, education: 13±3, sex: 52% male; HIV- age: 51±13, education: 14±2, sex: 48% male). HIV+ patients had worse cognitive performance than controls at both visits. NPZ8 was not associated with current or nadir CD4. No significant changes in NPZ8 were observed over time in either group. No differences in the change in NPZ8 between groups were detected. TBM revealed volume reductions in the thalamus, caudate, putamen, globus pallidus and midbrain in HIV+ patients at both visits. No significant changes in brain volume were observed over time in either group, and no differences in change in brain volume were detected between the groups. Brain volume measures were not correlated with NPZ8, current or nadir CD4.
Regionally specific subcortical volume reductions and poor cognitive performance were observed in the HIV+ group. However, no detectable brain volume loss or cognitive decline were revealed over 2 years in this sample of treated HIV+ patients. These findings support the hypothesis that brain dysfunction most likely occurs before cART initiation suggesting a possible neurocognitive benefit from early cART. Additional longitudinal studies with larger samples are warranted to validate these results.