Petkov, Stefan, Herrera, Carolina, Else, Laura, Mugaba, Susan, Namubiru, Patricia, Odoch, Geoffrey, Opoka, Daniel, Pillay, Azure-Dee AP, Seiphetlo, Thabiso B, Serwanga, Jennifer et al (show 9 more authors)
(2022)
Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa.
FRONTIERS IN IMMUNOLOGY, 13.
965214-.
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Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | emtricitabine tenofovir, prEP, young men, Sub-Saharan Africa, CCL4, CCL3 inflammatory cytokines |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 28 Oct 2022 14:46 |
| Last Modified: | 18 Jan 2023 19:48 |
| DOI: | 10.3389/fimmu.2022.965214 |
| Open Access URL: | https://doi.org/10.3389/fimmu.2022.965214 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165842 |
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