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Rosuvastatin Is Effective to Decrease CD8 T-Cell Activation Only in HIV-Infected Patients With High Residual T-Cell Activation Under Antiretroviral Therapy
Published by François RAFFI

Updated: 15 August, 2016

Weiss L et al. J Acquir Immune Defic Syndr. 2016 Apr 1;71(4):390-8

The aim of the trial was to evaluate in patients under ART the effect of rosuvastatin on cellular and soluble markers of immune activation/inflammation, as well as to identify patients who better benefit from statin administration.

IMEA-043-CESAR was a phase II open-label pilot trial that enrolled patients under suppressive ART and CD4 <500/mm3. Patients received rosuvastatin (20 mg/day) for 12 weeks. The primary outcome was the variation at W12 in the proportion of CD38+HLA-DR+CD8+ T lymphocytes. Secondary outcomes included evolution of other markers of T-cell activation and of inflammatory biomarkers between baseline, W12, and W24.

Fifty patients were enrolled; end points were available for 43 patients. The proportion of CD8 T cells coexpressing CD38 and HLA-DR did not change significantly at W12, with a median change of -10.4% (IQR, -38.5; +31) (P = 0.546). However, the proportion of CD38+CD8+T cells significantly decreased at W12 [median percentage change of -22.2% (-32.3; +1.4), p = 0.007]. Other CD8 T-cell activation markers did not change significantly. The proportion of activated CD4 T cells did not decrease from baseline to W12 or W24. CD4 and CD8 T-cell counts as well as the CD4/CD8 ratio did not change throughout the study. When considering the whole study population, there was no significant changes between baseline and W12 in the circulating levels of hsCRP, IL-6, sCD14, and D-dimers.
Principal component analysis allowed identification of 3 groups of patients based on their baseline activation/inflammation profiles, 1 group with elevated levels of CD8 T-cell activation and intermediate levels of inflammation biomarkers (“CD8 activated group”), and a small group with high levels of systemic inflammation and low levels of T-cell activation (“inflamed group”). Half of the patients exhibited relatively low levels of inflammation and activation despite incomplete CD4 cell recovery. The proportion of activated CD8 T cells significantly decreased only in the particular group of patients with high baseline CD8 T-cell activation.

In conclusion, combining rosuvastatin with effective ART can result in a sustained decrease in CD8 T-cell activation, highlighting the importance of identifying patients who can benefit from specific immunotherapeutic strategies.