Antiretroviral therapy reduces neurodegeneration in HIV infection.
Title | Antiretroviral therapy reduces neurodegeneration in HIV infection. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Bryant, AK, Ellis, RJ, Umlauf, A, Gouaux, B, Soontornniyomkij, V, Letendre, SL, Achim, CL, Masliah, E, Grant, I, Moore, DJ |
Journal | AIDS |
Volume | 29 |
Issue | 3 |
Pagination | 323-30 |
Date Published | 2015 Jan 28 |
ISSN | 1473-5571 |
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 | 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. |
DOI | 10.1097/QAD.0000000000000553 |
Alternate Journal | AIDS |
PubMed ID | 25686681 |
PubMed Central ID | PMC4353640 |
Grant List | U24 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 |