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

J Infect Dis. 2011 Mar 15;203(6):756-64. doi: 10.1093/infdis/jiq115. Epub 2011 Feb 15.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Atorvastatin
  • CD4-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Male
  • Placebos
  • Pyrroles / administration & dosage
  • Pyrroles / pharmacology*
  • RNA, Viral / blood
  • RNA, Viral / drug effects*

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Placebos
  • Pyrroles
  • RNA, Viral
  • Atorvastatin