# Influence of plasma exosomes from women living with HIV Stratified by HAND on monocyte subpopulations from healthy women without HIV

## TL;DR

This study explores how exosomes from HIV-positive women affect monocyte subpopulations, with implications for understanding HIV-associated neurocognitive disorders.

## Contribution

The study reveals time-dependent effects of HIV-positive exosomes on monocyte subsets and differences based on cognitive status.

## Key findings

- HIV-positive exosomes are taken up earlier by monocytes compared to HIV-negative exosomes.
- HIV-positive exosomes reduce classical monocytes and increase intermediate and nonclassical monocytes.
- Exosomes from normal cognition patients are taken up earlier and lead to higher monocyte subset percentages than those from SNI patients.

## Abstract

The role of plasma exosomes from people living with HIV (PLWH) with HAND in the phenotypic profile of uninfected monocytes remains unknown. We hypothesized that these exosomes influence the CD14/CD16 phenotypical profile of uninfected monocytes in a time-dependent manner. Exosomes were collected via ultracentrifugation from the plasma of women living with HIV (WLWH) and healthy controls stratified according to their cognition into normal cognition (NC) or symptomatic neurocognitive impairment (SNI) groups. Monocyte subsets were identified via flow cytometry by using anti-CD14 and anti-CD16 fluorescent antibodies. Exosome uptake and changes in the percentages of monocyte subpopulations were analyzed from 1 to 24 h. The following results were obtained. (1) The uptake of HIV-negative exosomes by total uninfected monocytes was observed at 24 h, whereas the uptake of HIV-positive exosomes was observed at an earlier time point at 6 h. (2) HIV-positive exosomes significantly decreased the percentage of classical monocytes and increased intermediate and nonclassical monocytes at 24 h. (3) The uptake of NC exosomes was observed at an early time point at 6 h compared with SNI in all of the monocyte subsets. (4) Higher percentages of monocyte subsets were observed when cells were exposed to NC exosomes at 1 h, 6 h, or 24 h than when monocytes were exposed to exosomes from SNI patients. Our findings may help to identify new targets and molecular mechanisms that are involved in the pathogenesis of HAND.