title: Atorvastatin reduces T-cell activation and exhaustion among HIV-infected cART-treated suboptimal immune responders in Uganda: a randomised crossover placebo-controlled trial.
abstract: OBJECTIVE
  T-cell activation independently predicts mortality, poor immune recovery and non-AIDS illnesses during combination antiretroviral therapy (cART). Atorvastatin showed anti-immune activation effects among HIV-infected cART-naïve individuals. We investigated whether adjunct atorvastatin therapy reduces T-cell activation among cART-treated adults with suboptimal immune recovery.
  
  
  METHODS
  A randomised double-blind placebo-controlled crossover trial, of atorvastatin 80 mg daily vs. placebo for 12 weeks, was conducted among individuals with CD4 increase <295 cells/μl after seven years of suppressive cART. Change in T-cell activation (CD3 + CD4 + /CD8 + CD38 + HLADR+) and in T-cell exhaustion (CD3 + CD4 + /CD8 + PD1 + ) was measured using flow cytometry.
  
  
  RESULTS
  Thirty patients were randomised, 15 to each arm. Atorvastatin resulted in a 28% greater reduction in CD4 T-cell activation (60% reduction) than placebo (32% reduction); P = 0.001. Atorvastatin also resulted in a 35% greater reduction in CD8-T-cell activation than placebo (49% vs. 14%, P = 0.0009), CD4 T-cell exhaustion (27% vs. 17% in placebo), P = 0.001 and CD8 T-cell exhaustion (27% vs. 16%), P = 0.004. There was no carry-over/period effect. Expected adverse events were comparable in both groups, and no serious adverse events were reported.
  
  
  CONCLUSIONS
  Atorvastatin reduced T-cell immune activation and exhaustion among cART-treated adults in a Ugandan cohort. Atorvastatin adjunct therapy should be explored as a strategy to improve HIV treatment outcomes among people living with HIV in sub-Saharan Africa.
authors.affiliation: Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
authors.forename: Damalie
authors.initials: D
authors.lastname: Nakanjako
authors.forename: Isaac
authors.initials: I
authors.lastname: Ssinabulya
authors.forename: Rose
authors.initials: R
authors.lastname: Nabatanzi
authors.forename: Lois
authors.initials: L
authors.lastname: Bayigga
authors.forename: Agnes
authors.initials: A
authors.lastname: Kiragga
authors.forename: Moses
authors.initials: M
authors.lastname: Joloba
authors.forename: Pontiano
authors.initials: P
authors.lastname: Kaleebu
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Kambugu
authors.forename: Moses R
authors.initials: MR
authors.lastname: Kamya
authors.forename: Rafick
authors.initials: R
authors.lastname: Sekaly
authors.forename: Alison
authors.initials: A
authors.lastname: Elliott
authors.forename: Harriet
authors.initials: H
authors.lastname: Mayanja-Kizza
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D015331:Cohort Studies; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D014454:Uganda; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin
keywords: HIV/AIDS; VIH/SIDA; activación inmune; activation immunitaire; adjunct therapy; antiretroviral therapy; atorvastatin; atorvastatina; atorvastatine; immune activation; immune recovery; reconstitution immunitaire; recuperación inmune; terapia adjunta; terapia antirretroviral; thérapie antirétrovirale; traitement d'appoint