A Sex-Stratified Analysis of Monocyte Phenotypes Associated with HIV Infection in Uganda.

Moises A Huaman,Steven K Grinspoon,Manuel G Feria,Rashidah Nazzinda,Mark J Siedner,David A Zidar,Sophie Nalukwago,Chris T Longenecker,Cissy Kityo,Markella V Zanni

doi:10.3390/v13112135

Abstract

Women with HIV may experience higher rates of non-AIDS comorbidities compared to men with HIV, but the underlying mechanisms are not well understood. We investigated sex-related differences in the effects of HIV on monocyte phenotypes within the Ugandan Study of HIV effects on the Myocardium and Atherosclerosis (mUTIMA). Of 133 participants who provided blood for flow cytometry assays, 86 (65%) were women and 91 (68%) were persons living with HIV (PLWH) on antiretroviral therapy. The median age was 57 (interquartile range, 52–63) years. PLWH exhibited a lower proportion of circulating CD14+CD16- classical monocytes (66.3% vs. 75.1%; p < 0.001), and higher proportion of CD14+CD16+ inflammatory monocytes (17% vs. 11.7%; p = 0.005) compared to HIV-uninfected participants. PLWH had an increased expression of the chemokine receptor CX3CR1 in total monocytes (CX3CR1+ monocytes, 24.5% vs. 4.7%; p < 0.001) and monocyte subsets. These findings were generally similar when analyzed by sex, with no significant interactions between sex and HIV status in adjusted models. Our data show that the inflammatory monocyte subset is expanded and monocyte CX3CR1 chemokine receptor expression is enhanced among PLWH, regardless of sex. Whether these parameters differentially affect risk for non-AIDS comorbidities and clinical outcomes in women with HIV requires additional investigation.

Highlights

Persons living with HIV (PLWH) have enhanced systemic inflammation and immune activation compared to the general population [1,2,3]
In terms of HIV status effects, we found higher proportions of CX3CR1 expression on monocytes compared to to persons without HIV (PWOH), PWOH, even even after after accounting accounting for on monocytes of of persons living with HIV (PLWH)
In this study, conducted among middle- and older-age women and men living in sub-Saharan Africa, we found that PLWH have an expanded proportion of inflammatory monocytes compared to PWOH

Summary

Introduction

Persons living with HIV (PLWH) have enhanced systemic inflammation and immune activation compared to the general population [1,2,3]. This persistent immune activation has been associated with increased morbidity and mortality due to noncommunicable diseases, including cardiovascular diseases, neurocognitive disorders, and non-AIDS cancers, even among PLWH with virologic suppression on antiretroviral therapy (ART) [2,4,5,6,7,8]. Due to the implication of monocyte alterations in the pathogenesis of non-AIDS comorbidities in PLWH [6,10], we analyzed potential sex differences in the phenotype of these immune cells. Prior reports demonstrated that the proportion of CD16+ monocyte subsets is increased in PLWH, including

Objectives

Methods

Results

Conclusion