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Sex differences in soluble markers vary before and after the initiation of antiretroviral therapy in chronically HIV-infected individuals

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Objective:

To evaluate differences in soluble inflammatory markers between chronically HIV-infected men and women, with or without cognitive impairment, and in response to treatment.

Design:

Soluble biomarkers were measured in cryopreserved plasma and cerebrospinal fluid (CSF) of 60 treatment-naïve individuals (25 men and 35 women) with chronic HIV infection and 18 HIV-uninfected controls (9 men and 9 women) from Thailand. Following enrollment, participants began combination antiretroviral therapy and were evaluated for expression of these markers after 48 weeks.Methods:

Plasma and CSF levels of 19 soluble biomarkers (IFN-γ, TNFα, TNF-RII, IL-1α, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-15, MCP-1, t-Tau, IP-10, neopterin, IFNα, I-FABP, and sCD14) were measured using either a multiparameter or standard ELISA assay.Results:

Prior to combination antiretroviral therapy, women with impaired cognition had elevated levels of neopterin and TNF-RII compared with women with normal cognition in both the plasma and CSF; however, levels did not differ between cognitively impaired or normal men. In a secondary outcome-hypothesis generating analysis, sex differences were also pronounced in plasma levels of MCP-1, IL-10, I-FABP, and sCD14 in response to treatment. Neopterin, IP-10, TNFα, TNF-RII, IFNα, MCP-1, IL-8, I-FABP, and sCD14 plasma levels remained elevated following 48 weeks of therapy in both sexes compared with uninfected controls.Conclusion:

We provide evidence of sustained immune activation after 48 weeks of treatment and identify possible sex differences in biomarkers previously linked to cognitive impairment, chronic inflammation, and gut integrity that may contribute to immunological differences between sexes in relationship to disease progression and response to therapy.

Keywords: HIV; cognition; cytokines; neopterin; sCD14; sex; soluble factors

Document Type: Research Article

Affiliations: 1: US Military HIV Research Program, Silver Spring, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA, Shelly J. Krebs and Bonnie M. Slike contributed equally to the writing of this article. 2: Phramongkutklao Hospital, Bangkok, Thailand 3: Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA 4: SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand 5: US Military HIV Research Program, Silver Spring 6: Currently, International Vaccine Institute, Seoul, Korea 7: US Military HIV Research Program, Silver Spring, Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA, SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand, Chulalongkorn University, Bangkok, Thailand 8: US Military HIV Research Program, Silver Spring, Currently, Vaccine Research and Development Section, Division of AIDS, NIH, Bethesda, Maryland 9: Department of Neurology, Memory and Aging Center, University of California, San Francisco, California, USA.

Publication date: 19 June 2016

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