Association of antiretroviral therapy with brain aging changes among HIV-infected adults.

TitleAssociation of antiretroviral therapy with brain aging changes among HIV-infected adults.
Publication TypeJournal Article
Year of Publication2018
AuthorsSoontornniyomkij, V, Umlauf, A, Soontornniyomkij, B, Gouaux, B, Ellis, RJ, Levine, AJ, Moore, DJ, Letendre, SL
Date Published2018 09 10
KeywordsAdolescent, Adult, Aged, Aged, 80 and over, Aging, Anti-Retroviral Agents, Antiretroviral Therapy, Highly Active, Brain, Darunavir, HIV Infections, Humans, Middle Aged, Neurodegenerative Diseases, Ritonavir, Young Adult

OBJECTIVE: Antiretroviral therapy (ART) is currently recommended for all persons living with HIV (PLWH), regardless of their CD4 T-cell count, and should be continued throughout life. Nonetheless, vigilance of the safety of ART, including its neurotoxicity, must continue. We hypothesized that use of certain ART drugs might be associated with aging-related cerebral degenerative changes among PLWH.DESIGN: Clinicopathological study of PLWH who were using ART drugs at the last clinical assessment.METHODS: Using multivariable logistic regression, we tested associations between use of each specific ART drug (with reference to use of other ART drugs) and cerebral degenerative changes including neuronal phospho-tau lesions, β-amyloid plaque deposition, microgliosis, and astrogliosis in the frontal cortex and putamen (immunohistochemistry), as well as cerebral small vessel disease (CSVD) in the forebrain white matter (standard histopathology), with relevant covariates being taken into account. The Bonferroni adjustment was applied.RESULTS: Darunavir use was associated with higher likelihood of neuronal phospho-tau lesions in the putamen [odds ratio (OR) 15.33, n = 93, P = 0.005]. Ritonavir use was associated with marked microgliosis in the putamen (OR 4.96, n = 101, P = 0.023). On the other hand, use of tenofovir disoproxil fumarate was associated with lower likelihood of β-amyloid plaque deposition in the frontal cortex (OR 0.13, n = 102, P = 0.012). There was a trend toward an association between emtricitabine use and CSVD (OR 13.64, n = 75, P = 0.099).CONCLUSION: Our findings suggest that PLWH treated with darunavir and ritonavir may be at increased risk of aging-related cerebral degenerative changes.

Alternate JournalAIDS
PubMed ID29912063
PubMed Central IDPMC6115290
Grant ListU24 MH100929 / MH / NIMH NIH HHS / United States
U24 MH100925 / MH / NIMH NIH HHS / United States
K24 MH097673 / MH / NIMH NIH HHS / United States
P50 DA026306 / DA / NIDA NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
R01 MH096648 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
U24 MH100930 / MH / NIMH NIH HHS / United States
R56 AG059437 / AG / NIA NIH HHS / United States