title: High dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial.
abstract: BACKGROUND
  3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins) exhibit antiviral activity against human immunodeficiency virus type 1 (HIV-1) in vitro and may modulate the immune response to HIV infection. Studies evaluating the antiviral activity of statins have yielded conflicting results.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled crossover trial to investigate the effect of atorvastatin on HIV-1 RNA (primary objective) and cellular markers of immune activation (secondary objective). HIV-infected individuals not receiving antiretroviral therapy were randomized to receive either 8 weeks of atorvastatin (80 mg) or placebo daily. After a 4-6 week washout phase, participants switched treatment assignments. The study had 80% power to detect a 0.3 log(10) decrease in HIV-1 RNA level. Expression of CD38 and HLA-DR on CD4(+) and CD8(+) T cells was used to measure immune activation.
  
  
  RESULTS
  Of 24 randomized participants, 22 completed the study. Although HIV-1 RNA level was unaffected by the intervention (-0.13 log(10) copies/mL; P = .85), atorvastatin use resulted in reductions in circulating proportions of CD4(+) HLA-DR(+) (-2.5%; P = .02), CD8(+) HLA-DR(+) (-5%; P = .006), and CD8(+) HLA-DR(+) CD38(+) T cells (-3%; P = .03). Reductions in immune activation did not correlate with declines in serum levels of low-density lipoprotein cholesterol.
  
  
  CONCLUSIONS
  Short-term use of atorvastatin was associated with modest but statistically significant reductions in the proportion of activated T lymphocytes.
authors.affiliation: Division of Infectious Diseases, National Naval Medical Center, Uniformed Services University, Bethesda, Maryland, USA. anuradha.ganesan@med.navy.mil
authors.forename: Anuradha
authors.initials: A
authors.lastname: Ganesan
authors.forename: Nancy
authors.initials: N
authors.lastname: Crum-Cianflone
authors.forename: Jeanette
authors.initials: J
authors.lastname: Higgins
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.forename: Catherine
authors.initials: C
authors.lastname: Rehm
authors.forename: Julia
authors.initials: J
authors.lastname: Metcalf
authors.forename: Carolyn
authors.initials: C
authors.lastname: Brandt
authors.forename: Jean
authors.initials: J
authors.lastname: Vita
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Decker
authors.forename: Peter
authors.initials: P
authors.lastname: Sklar
authors.forename: Mary
authors.initials: M
authors.lastname: Bavaro
authors.forename: Sybil
authors.initials: S
authors.lastname: Tasker
authors.forename: Dean
authors.initials: D
authors.lastname: Follmann
authors.forename: Frank
authors.initials: F
authors.lastname: Maldarelli
mesh_terms: D000328:Adult; D000069059:Atorvastatin; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010919:Placebos; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology*; D012367:RNA, Viral / Q000097:blood / Q000187:drug effects*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D011758:Pyrroles; D012367:RNA, Viral; D000069059:Atorvastatin