Antiretroviral therapy reduces neurodegeneration in HIV infection

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 treatmentmediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes.