Cenicriviroc, a dual CCR2 and CCR5 antagonist leads to a reduction in plasma fibrotic biomarkers in persons living with HIV on antiretroviral therapy

Abstract

Background: Chronic HIV is associated with increased inflammation and tissue fibrosis despite suppressive antiretroviral therapy (ART). Monocytes and macrophages have been implicated in the pathogenesis of fibrosis, facilitated by chemokine receptor interactions. Methods: We assessed systemic fibrotic biomarkers (transforming growth factor beta-1 [TGF-β1], thrombospondin-1 [TSP-1], C-terminal pro-peptide of collagen type I [CICP], and IL-11) in banked plasma from a previously published 24-week open-label trial of cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, among persons living with HIV (PLWH) on stable ART with undetectable plasma HIV RNA ( 0.05), while TSP-1 remained elevated in PLWH (p = 0.009) compared to controls. Conclusions: PLWH had higher levels of the plasma fibrotic markers TGF-β1, TSP-1, and CICP. After 24 weeks of CVC, fibrotic markers generally returned to levels comparable to HIV-uninfected controls. Dual CCR2 and CCR5 blockade may ameliorate the detrimental fibrotic events that persist in treated HIV.

Keywords

• hiv
• inflammation
• fibrosis
• chemokines
• ccr2
• ccr5