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Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa

HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during th...

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Autores principales: Petkov, Stefan, Herrera, Carolina, Else, Laura, Mugaba, Susan, Namubiru, Patricia, Odoch, Geoffrey, Opoka, Daniel, Pillay, Azure-Dee A. P., Seiphetlo, Thabiso B., Serwanga, Jennifer, Ssemata, Andrew S., Kaleebu, Pontiano, Webb, Emily L., Khoo, Saye, Lebina, Limakatso, Gray, Clive M., Martinson, Neil, Fox, Julie, Chiodi, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363563/
https://www.ncbi.nlm.nih.gov/pubmed/35967369
http://dx.doi.org/10.3389/fimmu.2022.965214
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author Petkov, Stefan
Herrera, Carolina
Else, Laura
Mugaba, Susan
Namubiru, Patricia
Odoch, Geoffrey
Opoka, Daniel
Pillay, Azure-Dee A. P.
Seiphetlo, Thabiso B.
Serwanga, Jennifer
Ssemata, Andrew S.
Kaleebu, Pontiano
Webb, Emily L.
Khoo, Saye
Lebina, Limakatso
Gray, Clive M.
Martinson, Neil
Fox, Julie
Chiodi, Francesca
author_facet Petkov, Stefan
Herrera, Carolina
Else, Laura
Mugaba, Susan
Namubiru, Patricia
Odoch, Geoffrey
Opoka, Daniel
Pillay, Azure-Dee A. P.
Seiphetlo, Thabiso B.
Serwanga, Jennifer
Ssemata, Andrew S.
Kaleebu, Pontiano
Webb, Emily L.
Khoo, Saye
Lebina, Limakatso
Gray, Clive M.
Martinson, Neil
Fox, Julie
Chiodi, Francesca
author_sort Petkov, Stefan
collection PubMed
description HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during the CHAPS trial in South Africa and Uganda (NCT03986970). The CHAPS trial randomized 144 participants to one control and 8 PrEP arms, differing by drug type, number of PrEP doses and timing from final PrEP dose to sampling. Blood was collected pre- and post-PrEP. The inflammatory profile of plasma samples was analyzed using Olink (N=92 proteins) and Luminex (N=33) and associated with plasma drug concentrations using mass spectrometry. The proteins whose levels changed most significantly from pre- to post-PrEP were CCL4, CCL3 and TNF-α; CCL4 was the key discriminator between pre- and post-PrEP samples. CCL4 and CCL3 levels were significantly increased in post-PrEP samples compared to control specimens. CCL4 was significantly correlated with FTC drug levels in plasma. Production of inflammatory chemokines CCL4 and CCL3 in response to short-term PrEP indicates the mobilization of ligands which potentially block virus attachment to CCR5 HIV-1 co-receptor. The significant correlation between CCL4 and FTC levels suggests that CCL4 increase is modulated as an inflammatory response to PrEP.
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spelling pubmed-93635632022-08-11 Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa Petkov, Stefan Herrera, Carolina Else, Laura Mugaba, Susan Namubiru, Patricia Odoch, Geoffrey Opoka, Daniel Pillay, Azure-Dee A. P. Seiphetlo, Thabiso B. Serwanga, Jennifer Ssemata, Andrew S. Kaleebu, Pontiano Webb, Emily L. Khoo, Saye Lebina, Limakatso Gray, Clive M. Martinson, Neil Fox, Julie Chiodi, Francesca Front Immunol Immunology HIV-1 pre-exposure prophylaxis (PrEP) relies on inhibition of HIV-1 replication steps. To understand how PrEP modulates the immunological environment, we derived the plasma proteomic profile of men receiving emtricitabine-tenofovir (FTC-TDF) or emtricitabine-tenofovir alafenamide (FTC-TAF) during the CHAPS trial in South Africa and Uganda (NCT03986970). The CHAPS trial randomized 144 participants to one control and 8 PrEP arms, differing by drug type, number of PrEP doses and timing from final PrEP dose to sampling. Blood was collected pre- and post-PrEP. The inflammatory profile of plasma samples was analyzed using Olink (N=92 proteins) and Luminex (N=33) and associated with plasma drug concentrations using mass spectrometry. The proteins whose levels changed most significantly from pre- to post-PrEP were CCL4, CCL3 and TNF-α; CCL4 was the key discriminator between pre- and post-PrEP samples. CCL4 and CCL3 levels were significantly increased in post-PrEP samples compared to control specimens. CCL4 was significantly correlated with FTC drug levels in plasma. Production of inflammatory chemokines CCL4 and CCL3 in response to short-term PrEP indicates the mobilization of ligands which potentially block virus attachment to CCR5 HIV-1 co-receptor. The significant correlation between CCL4 and FTC levels suggests that CCL4 increase is modulated as an inflammatory response to PrEP. Frontiers Media S.A. 2022-07-27 /pmc/articles/PMC9363563/ /pubmed/35967369 http://dx.doi.org/10.3389/fimmu.2022.965214 Text en Copyright © 2022 Petkov, Herrera, Else, Mugaba, Namubiru, Odoch, Opoka, Pillay, Seiphetlo, Serwanga, Ssemata, Kaleebu, Webb, Khoo, Lebina, Gray, Martinson, Fox and Chiodi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Petkov, Stefan
Herrera, Carolina
Else, Laura
Mugaba, Susan
Namubiru, Patricia
Odoch, Geoffrey
Opoka, Daniel
Pillay, Azure-Dee A. P.
Seiphetlo, Thabiso B.
Serwanga, Jennifer
Ssemata, Andrew S.
Kaleebu, Pontiano
Webb, Emily L.
Khoo, Saye
Lebina, Limakatso
Gray, Clive M.
Martinson, Neil
Fox, Julie
Chiodi, Francesca
Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa
title Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa
title_full Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa
title_fullStr Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa
title_full_unstemmed Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa
title_short Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa
title_sort mobilization of systemic ccl4 following hiv pre-exposure prophylaxis in young men in africa
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363563/
https://www.ncbi.nlm.nih.gov/pubmed/35967369
http://dx.doi.org/10.3389/fimmu.2022.965214
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