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:
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Authors | Daniel E Nixon, Ronald J Bosch, Ellen S Chan, Nicholas T Funderburg, Sally Hodder, Jordan E Lake, Michael M Lederman, Karin L Klingman, Judith A Aberg, AIDS Clinical Trials Group Study A5275 Team |
Journal | Journal of clinical lipidology
(J Clin Lipidol)
2017 Jan - Feb
Vol. 11
Issue 1
Pg. 61-69
ISSN: 1933-2874 [Print] United States |
PMID | 28391912
(Publication Type: Journal Article, Randomized Controlled Trial)
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Copyright | Copyright © 2016 National Lipid Association. All rights reserved. |
Chemical References |
- Biomarkers
- Cholesterol, LDL
- Kruppel-Like Transcription Factors
- Lipids
- Atorvastatin
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Topics |
- Adult
- Atorvastatin
(adverse effects, pharmacology, therapeutic use)
- Biomarkers
(blood)
- Cholesterol, LDL
(blood)
- Female
- HIV Infections
(blood, drug therapy, immunology)
- HIV-1
(physiology)
- Humans
- Inflammation
(blood)
- Kruppel-Like Transcription Factors
(blood)
- Lipids
(blood)
- Male
- Middle Aged
- Safety
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