In vitro and animal studies revealed a potential protective role of CCR5 antagonists on reducing liver fibrosis progression and protecting from developing hepatocellular carcinoma.1 Hepatocytes bear CXCR4 and CCR5, the 2 main coreceptors for HIV entry into cells and the blockade of coreceptors on hepatic stellate cells, the major producers of extracellular matrix in the liver, will slow progression of liver fibrosis, especially due to HIV-envelope gp120–mediated fibrogenesis modulation.2–5
The aim of present analysis was to compare the evolution of liver fibrosis over time evaluated by surrogated biomarker assays in HIV-1–infected patients on a virologically successful antiretroviral therapy (stable HIV-1 RNA <50 copies/mL), randomized to switch to maraviroc + darunavir/r (MVC + DRV/r arm) qd or to continue the current MVC-free 3-drug antiretroviral therapy (ART) (3-drug ART arm).
Patients included in the study were enrolled in the GUided Simplification with Tropism Assay (GUSTA) trial, a multicenter, open-label, randomized study (www.clinicaltrials.gov, number NCT01367210), whose main results have been published.6
Briefly, GUSTA included patients with HIV-1 RNA <50 copies/mL for at least 6 months, R5 tropism and CD4 counts >200 cells/μL for at least 3 months before enrollment; hepatitis B virus–coinfected patients and those with Child-Pugh B/C cirrhosis were excluded.
We retrospectively evaluated Fibrosis-4 (FIB-4) Index and aspartate aminotransferase to Platelet Ratio Index (APRI) scores, at baseline and after 12, 24, 48, and 96 weeks. The cutoff points of serum marker tests of hepatic fibrosis were as follows: FIB-4 <1.45 (F0-F1), 1.45–3.25 (indeterminate), and >3.25 (F3-F4); APRI <0.5 (F0-F1), >1.5 (F2) and >2 (cirrhosis).
Differences between arms were assessed by χ2 and Student t test, longitudinal within-group differences by McNemar test. The FIB-4 Index and APRI scores were used as continuous variables; their predictors at baseline and their change over time were investigated by linear regression.