Antiretroviral therapy reduces neurodegeneration in HIV infection. (28th January 2015)

• Record Type: Journal Article
• Authors: Bryant, Alex K.; Ellis, Ronald J.; Umlauf, Anya; Gouaux, Ben; Soontornniyomkij, Virawudh; Letendre, Scott L.; Achim, Cristian L.; Masliah, Eliezer; Grant, Igor; Moore, David J.
• Is Part Of: AIDS. Volume 29:Number 3(2015)
• Publication Date: 2015-01-28
• Subjects: AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000000553
• Languages: English
• ISSNs: 0269-9370

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective:</title> <p>To determine the effect of virally suppressive antiretroviral therapy (ART) on cortical neurodegeneration and associated neurocognitive impairment.</p> </sec> <sec> <title>Design:</title> <p>Retrospective, postmortem observational study.</p> </sec> <sec> <title>Methods:</title> <p>Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 HIV-infected volunteers from the general community who had never undergone ART (<italic>n</italic> = 7, 'naive') or who had undergone ART and whose plasma viral load was detectable (<italic>n</italic> = 64 'unsuppressed') or undetectable (<italic>n</italic> = 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.</p> </sec> <sec> <title>Results:</title> <p>The suppressed group had higher SYP density than the naive group (<italic>P</italic> = 0.007) and higher MAP2 density than the unsuppressed group (<italic>P</italic> = 0.04). The suppressed group had lower odds of HIV-associated neurocognitive disorders than naive [odds ratio (OR) 0.07, <italic>P</italic> = 0.03]. Higher SYP was associated with lower likelihood of HIV-associated neurocognitive disorders in univariable (OR 0.8, <italic>P</italic> = 0.03) and multivariable models after controlling for ART and brain HIV p24 protein levels (OR 0.72, <italic>P</italic> = 0.01).</p> </sec> <sec> <title>Conclusion:</title> <p>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> </sec> </abstract>