Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa
Male
Proteomics
0301 basic medicine
TENOFOVIR DISOPROXIL FUMARATE
Anti-HIV Agents
Immunology
610
CCL3 inflammatory cytokines
HIV Infections
South Africa
03 medical and health sciences
0302 clinical medicine
1108 Medical Microbiology
616
HIV Seropositivity
Emtricitabine
Humans
Chemokine CCL4
Chemokine CCL3
CCL4
Science & Technology
Sub-Saharan Africa
RC581-607
emtricitabine tenofovir
prEP
HIGH-RISK
1107 Immunology
HIV-1
EMTRICITABINE
Pre-Exposure Prophylaxis
Immunologic diseases. Allergy
Life Sciences & Biomedicine
young men
DOI:
10.3389/fimmu.2022.965214
Publication Date:
2022-07-27T04:44:33Z
AUTHORS (19)
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.
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CITATIONS (5)
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