BASIC SCIENCEMonocyte and CD4+ T-cell antiviral and innate responses associated with HIV-1 inflammation and cognitive impairmentSharma, Vishakhaa,b; Bryant, Christopherc; Montero, Mariaa,b,∗; Creegan, Matthewa,b; Slike, Bonniea,b; Krebs, Shelly J.a,b; Ratto-Kim, Silviaa,b,†; Valcour, Victord; Sithinamsuwan, Pasirie; Chalermchai, Thepf; Eller, Michael A.a,b; Bolton, Diane L.a,b; on behalf of the SEARCH007/SEARCH011 Study GroupsfAuthor Information aU.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring bHenry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda cThe EMMES Corporation, Rockville, Maryland dMemory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, California, USA eFaculty of Medicine, Phramongkutklao Hospital fSEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand. Correspondence to Diane L. Bolton, U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA. E-mail: firstname.lastname@example.org Received 27 September, 2019 Revised 18 March, 2020 Accepted 18 March, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). AIDS: July 15, 2020 - Volume 34 - Issue 9 - p 1289-1301 doi: 10.1097/QAD.0000000000002537 Buy SDC Metrics Abstract Objective: Mechanisms underlying immune activation and HIV-associated neurocognitive disorders (HAND) in untreated chronic infection remain unclear. The objective of this study was to identify phenotypic and transcriptional changes in blood monocytes and CD4+ T cells in HIV-1-infected and uninfected individuals and elucidate processes associated with neurocognitive impairment. Design: A group of chronically HIV-1-infected Thai individuals (n = 19) were selected for comparison with healthy donor controls (n = 10). Infected participants were further classified as cognitively normal (n = 10) or with HAND (n = 9). Peripheral monocytes and CD4+ T cells were phenotyped by flow cytometry and simultaneously isolated for multiplex qPCR-targeted gene expression profiling directly ex vivo. The frequency of HIV-1 RNA-positive cells was estimated by limiting dilution cell sorting. Results: Expression of genes and proteins involved in cellular activation and proinflammatory immune responses was increased in monocytes and CD4+ T cells from HIV-1-infected relative to uninfected individuals. Gene expression profiles of both CD4+ T cells and monocytes correlated with soluble markers of inflammation in the periphery (P < 0.05). By contrast, only modest differences in gene programs were observed between cognitively normal and HAND cases. These included increased monocyte surface CD169 protein expression relative to cognitively normal (P = 0.10), decreased surface CD163 expression relative to uninfected (P = 0.02) and cognitively normal (P = 0.06), and downregulation of EMR2 (P = 0.04) and STAT1 (P = 0.02) relative to cognitively normal. Conclusion: Our data support a model of highly activated monocytes and CD4+ T cells associated with inflammation in chronic HIV-1 infection, but impaired monocyte anti-inflammatory responses in HAND compared with cognitively normal. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.