Abstract

ObjectivesGender-specific studies remain a neglected area of biomedical research. Recent reports have emphasized that sex-related biological factors may affect disease progression during HIV-1 infection. The aim of this study was to investigate the influence of sex on the levels of immune activation in the gut and in peripheral blood of individuals with HIV treated with fully suppressive antiretroviral therapy (ART).MethodsThirty individuals with HIV undergoing long-term fully suppressive ART were enrolled in this study. Lamina propria lymphocytes (LPL) and peripheral blood mononuclear cells (PBMCs) were isolated from gut biopsies collected by pancolonoscopy and peripheral blood samples. The expression of markers of immune activation was evaluated by multi-parametric flow cytometry. This is a sub analysis of ClinicalTrials.gov Identifier: NCT02276326ResultsWe observed differences in the levels of immune activation in the gut and in PBMCs, with values higher in the gut compartment compared to PBMCs.In addition, we found that the mean value of the levels of immune activation was higher in the women than in the men. Finally, we measured the markers of immune activation by mean relative difference (MRD) and confirmed the higher value in the women.ConclusionA significant sex-related difference in the level of immune activation was observed in a population of individuals with HIV on long-term ART. A more complete characterization of these differences may support the introduction of sex-specific approaches in the clinical management of individuals with HIV.

Highlights

  • In 2015, the National Institutes of Health (NIH) established that sex is a biological variable (SABV) to take into account for NIH funding and scientific publication [1]

  • The blood sample collection by venepuncture was performed in all subjects enrolled: whole blood was collected in vacutainer tubes containing ethylenediaminetetraacetic acid (BD Biosciences, San Jose, CA), and peripheral blood mononuclear cells (PBMCs) were separated by Ficoll gradient centrifugation (Lympholyte, Cedarlane Labs, Hornby, Ontario, Canada), followed by two washes in phosphatebuffered saline

  • They were started on antiretroviral therapy (ART) during chronic HIV-1 infection with a median CD4 T-cell count of 300 at the beginning of therapy (IQR 115-377)

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Summary

Introduction

In 2015, the National Institutes of Health (NIH) established that sex is a biological variable (SABV) to take into account for NIH funding and scientific publication [1]. This statement was based on scientific evidence that sex affects innate and adaptive immunity and results in. Several studies revealed lower viremia in the initial phase of chronic HIV infection in women as compared to men (over 40% less circulating HIV RNA than men) [7]. Changes in the levels of soluble markers of immune activation were reported in woman and men with chronic HIV infection, suggesting a potential predictive role in terms of HIV disease outcome [10]

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