Mobilization of systemic CCL4 following HIV pre-exposure prophylaxis in young men in Africa.
Front Immunol
; 13: 965214, 2022.
Article
em En
| MEDLINE
| ID: mdl-35967369
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Soropositividade para HIV
/
Fármacos Anti-HIV
/
Quimiocina CCL4
/
Profilaxia Pré-Exposição
/
Emtricitabina
Tipo de estudo:
Clinical_trials
Limite:
Humans
/
Male
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article