Higher CCR5 density on CD4 + T-cells in mothers and infants is associated with increased risk of in-utero HIV-1 transmission.

AIDS

Centre for HIV and STIs, National Institute for Communicable Diseases, a division of the National Health Laboratory Service, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Published: June 2024

Objective: CCR5-tropic viruses are preferentially transmitted during perinatal HIV-1 infection. CCR5 density on CD4 + T-cells likely impacts susceptibility to HIV-1 infection.

Design: Fifty-two mother-infant dyads were enrolled. All mothers were living with HIV-1, 27 of the infants acquired HIV-1 in utero and 25 infants remained uninfected.

Methods: CCR5 density, together with frequencies of CD4 + and CD8 + T-cells expressing immune activation (CCR5, ICOS and HLA-DR) and immune checkpoint (TIGIT and PD-1) markers, were measured in whole blood from the dyads close to delivery.

Results: Compared with mothers who did not transmit, mothers who transmitted HIV-1 had less exposure to ART during pregnancy ( P = 0.015) and higher plasma viral load close to delivery ( P = 0.0005). These mothers, additionally, had higher CCR5 density on CD4 + and CD8 + T-cells and higher frequencies of CCR5, ICOS and TIGIT-expressing CD8 + T-cells. Similarly, compared with infants without HIV-1, infants with HIV-1 had higher CCR5 density on CD4 + and CD8 + T-cells and higher frequencies of CCR5, TIGIT, and PD-1-expressing CD4 + and CD8 + T-cells as well as higher frequencies of HLA-DR-expressing CD8 + T-cells. CCR5 density on maternal CD4 + T-cells remained significantly associated with transmission after adjusting for maternal viral load and CD4 + T cell counts. Mother-infant dyads with shared high CCR5 density phenotypes had the highest risk of transmission/acquisition of infection compared with dyads with shared low-CCR5 density phenotypes.

Conclusion: This study provides strong evidence of a protective role for a combined mother-infant low CD4 + T-cell CCR5 density phenotype in in-utero transmission/acquisition of HIV-1.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11064911PMC
http://dx.doi.org/10.1097/QAD.0000000000003857DOI Listing

Publication Analysis

Top Keywords

ccr5 density
32
cd8 t-cells
24
density cd4
16
cd4 cd8
16
higher ccr5
12
cd4 t-cells
12
higher frequencies
12
ccr5
10
density
9
cd4
9

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!