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
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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