Antiretroviral therapy reduces neurodegeneration in HIV infection.

TitleAntiretroviral therapy reduces neurodegeneration in HIV infection.
Publication TypeJournal Article
Year of Publication2015
AuthorsBryant, AK, Ellis, RJ, Umlauf, A, Gouaux, B, Soontornniyomkij, V, Letendre, SL, Achim, CL, Masliah, E, Grant, I, Moore, DJ
Date Published2015 Jan 28
KeywordsAdult, 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

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.

Alternate JournalAIDS
PubMed ID25686681
PubMed Central IDPMC4353640
Grant ListU24 MH100929 / MH / NIMH NIH HHS / United States
P50 DA026306 / DA / NIDA NIH HHS / United States
U01 MH083500 / MH / NIMH NIH HHS / United States
R01 AG043384 / AG / NIA NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
R01 MH062962 / MH / NIMH NIH HHS / United States
P30MH062512 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
U01MH83506 / MH / NIMH NIH HHS / United States
U01 MH083506 / MH / NIMH NIH HHS / United States