Date Published:
2015 Jan 28
Publication Type:
Journal Article
Authors:
Secondary:
AIDS
Volume:
29
Pagination:
323-30
Issue:
3
PMID:
25686681
URL:
https://pubmed.ncbi.nlm.nih.gov/25686681
DOI:
10.1097/QAD.0000000000000553
Keywords:
Adult;Aged;Anti-Retroviral Agents;Autopsy;Cerebral Cortex;Female;HIV Infections;Humans;Internal;Male;Microtubule-Associated Proteins;Middle Aged;Neurodegenerative Diseases;Retrospective Studies;Synaptophysin;Treatment Outcome;Viral Load
Abstract:
<p>OBJECTIVE: To determine the effect of virally suppressive antiretroviral therapy (ART) on cortical neurodegeneration and associated neurocognitive impairment.DESIGN: Retrospective, postmortem observational study.METHODS: Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 HIV-infected volunteers from the general community who had never undergone ART (n = 7, 'naive') or who had undergone ART and whose plasma viral load was detectable (n = 64 'unsuppressed') or undetectable (n = 19, 'suppressed') at the last clinical visit before death. Individuals were predominately men (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections.RESULTS: The suppressed group had higher SYP density than the naive group (P = 0.007) and higher MAP2 density than the unsuppressed group (P = 0.04). The suppressed group had lower odds of HIV-associated neurocognitive disorders than naive [odds ratio (OR) 0.07, P = 0.03]. Higher SYP was associated with lower likelihood of HIV-associated neurocognitive disorders in univariable (OR 0.8, P = 0.03) and multivariable models after controlling for ART and brain HIV p24 protein levels (OR 0.72, P = 0.01).CONCLUSION: We conclude that virally suppressive ART protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes.</p>