Effects of atorvastatin on biomarkers of immune activation, inflammation, and lipids in virologically suppressed, human immunodeficiency virus-1-infected individuals with low-density lipoprotein cholesterol <130 mg/dL (AIDS Clinical Trials Group Study A5275)

J Clin Lipidol. Jan-Feb 2017;11(1):61-69. doi: 10.1016/j.jacl.2016.09.017. Epub 2016 Oct 5.

Abstract

Background: Persistent immune activation and inflammation in virologically suppressed human immunodeficiency virus (HIV) infection are linked to excess cardiovascular risk.

Objective: To evaluate atorvastatin as a strategy to reduce cardiovascular risk.

Methods: A5275 was a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over pilot study of atorvastatin (10 mg/day for 4 weeks then 20 mg/day for 16 weeks) with a planned enrollment of 97 HIV-infected participants ≥18 years old, receiving boosted protease inhibitor-based antiretroviral therapy for ≥6 months, with plasma HIV-1 RNAs below limits of quantification ≥180 days, and fasting low-density lipoprotein (LDL) cholesterol ≥70 and <130 mg/dL. Primary endpoints were differences of changes ([week 44-week 24]-[week 20-baseline]) in CD4+ and CD8+ T-lymphocyte activation (% CD38+/DR+) and plasma levels of IL-6 and D-dimer. Arms were compared using the Wilcoxon rank-sum tests and also summarized changes pre-to-post atorvastatin treatment. Analyses were as-treated.

Results: Ninety-eight participants were enrolled at 31 U S sites and 73 completed study treatment. Atorvastatin treatment did not decrease T-lymphocyte or monocyte activation, circulating biomarker levels (interleukin-6, D-dimer, soluble CD14, soluble CD163, monocyte chemoattractant protein-1, interferon-gamma-induced protein-10, high-sensitivity C-reactive protein, CD40L, and P-selectin) or white blood cell Krüppel-like Factor 2/4 messenger RNA levels. Pre-to-post atorvastatin reductions in calculated LDL (-38%), oxidized-LDL (-33%), and lipoprotein-associated phospholipase A2 (-31%) were significant (P < .01).

Conclusion: In virologically suppressed individuals with HIV infection, atorvastatin did not significantly decrease levels of soluble or cellular biomarkers of immune activation and inflammation but resulted in robust reductions in LDL cholesterol, oxLDL, and lipoprotein-associated phospholipase A2, biomarkers associated with cardiovascular risk.

Keywords: Cardiovascular; HIV; Immune activation; Inflammation; Oxidized LDL; Statin.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Atorvastatin / adverse effects
  • Atorvastatin / pharmacology*
  • Atorvastatin / therapeutic use
  • Biomarkers / blood
  • Cholesterol, LDL / blood*
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV-1 / physiology*
  • Humans
  • Inflammation / blood
  • Kruppel-Like Transcription Factors / blood
  • Lipids / blood*
  • Male
  • Middle Aged
  • Safety

Substances

  • Biomarkers
  • Cholesterol, LDL
  • Kruppel-Like Transcription Factors
  • Lipids
  • Atorvastatin