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

Soontornniyomkij, Virawudha,b; Umlauf, Anyaa; Soontornniyomkij, Benchawannab; Gouaux, Bena; Ellis, Ronald J.a,c; Levine, Andrew J.d; Moore, David J.a,b; Letendre, Scott L.a,e

doi: 10.1097/QAD.0000000000001927

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.

aHIV Neurobehavioral Research Program

bDepartment of Psychiatry

cDepartment of Neurosciences, School of Medicine, University of California San Diego, La Jolla

dDepartment of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles

eDepartment of Medicine, School of Medicine, University of California San Diego, La Jolla, California, USA.

Correspondence to Virawudh Soontornniyomkij, MD, Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603, USA. Tel: +1 858 822 4546; fax: +1 858 534 4484; e-mail:

Received 16 February, 2018

Revised 22 May, 2018

Accepted 23 May, 2018

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