Journal Article

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

Kaleebu, Pontiano, Mugaba, Susan, Martinson, Neil, Herrera, Carolina, Chiodi, Francesca, Webb, Emily L., Pillay, Azure-Dee A. P., Khoo, Saye, Namubiru, Patricia, Gray, Clive M., Ssemata, Andrew S., Opoka, Daniel, Lebina, Limakatso, Odoch, Geoffrey, Else, Laura, Petkov, Stefan, Seiphetlo, Thabiso B., Serwanga, Jennifer, Fox, Julie

2022

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Anti-HIV Agents - administration & dosage / Antiretroviral drugs / CCL3 inflammatory cytokines / CCL4 / CCL4 protein / Chemokine CCL3 / Chemokine CCL4 - drug effects / Chemokines / Cytokines / Disease prevention / Drug dosages / Emtricitabine / Emtricitabine - administration & dosage / emtricitabine tenofovir / HIV / HIV Infections - prevention & control / HIV Seropositivity / HIV-1 / Human immunodeficiency virus / Humans / Immunology / Infections / Inflammation / Male / Mass spectroscopy / Plasma / Pre-Exposure Prophylaxis - methods / prEP / Proteins / Proteomics / Research ethics / South Africa / Sub-Saharan Africa / Tenofovir / Tumor necrosis factor-α / Virus attachment / young men