Send to

Choose Destination
Clin Infect Dis. 2018 Sep 20. doi: 10.1093/cid/ciy807. [Epub ahead of print]

Improvement in Hepatic Fibrosis Biomarkers Associated with Chemokine Receptor Inactivation through Mutation or Therapeutic Blockade.

Author information

University of Cincinnati College of Medicine, Cincinnati, OH.
Research Triangle Institute, Philadelphia, PA.
Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
University of Maryland, Baltimore, MD.



CCR5 is a key receptor for HIV-1 viral entry into T-cells and a variant allele, CCR5 delta-32, is associated with decreased viral replication and disease progression. Active HIV-1 replication is highly associated with accelerated rates of hepatic fibrosis. We postulated that CCR5 plays a central role in the development of hepatic fibrosis, and evaluated the longitudinal effect of both natural or drug-induced CCR5 mutation and blockade on biomarkers of liver fibrosis in HIV-1 infected patients.


To accomplish this goal, we examined two distinct cohorts. First, we evaluated fibrosis markers in the Multicenter Hemophilia Cohort Studies (MCHS) which included subjects with HIV and HCV coinfection with the CCR5 delta-32 allele. We also evaluated an HIV-1 infected cohort that was treated with a dual CCR5/CCR2 antagonist, cenicriviroc. The Enhanced Liver Fibrosis (ELF) Index was validated against liver histology obtained from HCV/HIV coinfected and HCV monoinfected patients and demonstrated strong correlation with fibrosis stage.


In both the MHCS patients and among patients treated with cenicriviroc, CCR5 mutation or blockade was associated with a significant decrease in the validated fibrosis biomarker. Among the patients with the delta-32 allele, the ELF Index rate significantly decreased in sequential samples as compared to CCR5 wildtype patients (p = 0.043). This was not observed in control subjects treated with efavirenz nor with a lower dose of 100 mg CVC.


These finding strongly suggest that hepatic fibrosis in HIV-1 infected patients can be modulated by the mutation of CCR5 and/or use of CCR5/CCR2 blockade agents.


Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center