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

• DOI: 10.3389/fimmu.2022.965214
• Publication Date: 2022-07-27T04:44:33Z
• Authors: Stefan Petkov; Carolina Herrera; Laura Else; Susan Mugaba; Patricia Namubiru; Geoffrey Odoch; Daniel Opoka; Azure-Dee A. P. P...; Thabiso B. Seiphetlo; Jennifer Serwanga; Andrew S. Ssemata; Pontiano Kaleebu; Emily L. Webb; Saye Khoo; Limakatso Lebina; Clive M. Gray; Neil Martinson; Julie Fox; Francesca Chiodi
• Keywords: 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

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.