title: Rosuvastatin Is Effective to Decrease CD8 T-Cell Activation Only in HIV-Infected Patients With High Residual T-Cell Activation Under Antiretroviral Therapy.
abstract: OBJECTIVE
  The aim of the trial was to evaluate in patients under antiretroviral therapy (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.
  
  
  METHODS
  IMEA-043-CESAR was a phase II open-label pilot trial that enrolled patients under suppressive ART and CD4 <500/mm. Patients received rosuvastatin (20 mg/d) for 12 weeks. The primary outcome was the variation at week 12 (W12) in the proportion of CD38HLA-DRCD8 T lymphocytes. Secondary outcomes included evolution of other markers of T-cell activation and of inflammatory biomarkers between baseline, W12, and W24.
  
  
  RESULTS
  Fifty patients were enrolled; end points were available for 43 patients. When considering all patients, the proportion of CD38HLA-DRCD8 T cells did not significantly decline throughout the follow-up. However, the proportion of CD38CD8T cells significantly decreased at W12 [median percentage change of -22.2% (-32.3; +1.4)]. 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 a small group with high levels of systemic inflammation and low levels of T-cell activation. Half of the patients exhibited relatively low levels of inflammation and activation. The proportion of activated CD8 T cells significantly decreased only in the particular group of patients with high baseline CD8 T-cell activation.
  
  
  CONCLUSIONS
  This study shows that combining rosuvastatin with effective ART can result in a sustained decrease in CD8 T-cell activation and highlights the importance of identifying patients who can benefit from specific immunotherapeutic strategies.
authors.affiliation: *AP-HP Hôpital Européen Georges Pompidou, Paris, France; †Université Paris Descartes, Sorbonne Paris-Cité, Paris, France; ‡Institut Pasteur, Régulation des infections rétrovirales, Paris, France; §Currently Urology Research Unit, Lausanne University Hospital, Lausanne, Switzerland; ‖Sorbonne Universités, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; ¶INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; #Lip(Sys)2, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France; **Service de Biochimie, and ††Laboratoire d'Hématologie, AP-HP, Hôpital Européen Georges Pompidou, Paris, France; and ‡‡AP-HP Hôpital Saint-Antoine, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
authors.forename: Mathieu F
authors.initials: MF
authors.lastname: Chevalier
authors.forename: Lambert
authors.initials: L
authors.lastname: Assoumou
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paul
authors.forename: Martine
authors.initials: M
authors.lastname: Alhenc-Gelas
authors.forename: Céline
authors.initials: C
authors.lastname: Didier
authors.forename: Saïd
authors.initials: S
authors.lastname: Taibi
authors.forename: Elena-Maria
authors.initials: EM
authors.lastname: Manea
authors.forename: Pauline
authors.initials: P
authors.lastname: Campa
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001777:Blood Coagulation; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007249:Inflammation / Q000097:blood / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D000068718:Rosuvastatin Calcium / Q000494:pharmacology*; D014779:Virus Replication
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000068718:Rosuvastatin Calcium