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 A5

TitleEffects 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 A5
Publication TypeJournal Article
Year of Publication2017
AuthorsNixon DE, Bosch RJ, Chan ES, Funderburg NT, Hodder S, Lake JE, Lederman MM, Klingman KL, Aberg JA
Corporate AuthorsAIDS Clinical Trials Group Study A5275 Team
JournalJ Clin Lipidol
Volume11
Issue1
Pagination61-69
Date Published2017 Jan - Feb
ISSN1933-2874
KeywordsAdult, Atorvastatin Calcium, Biomarkers, Cholesterol, LDL, Female, HIV Infections, HIV-1, Humans, Inflammation, Kruppel-Like Transcription Factors, Lipids, Male, Middle Aged, Safety
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 A, biomarkers associated with cardiovascular risk.

DOI10.1016/j.jacl.2016.09.017
Alternate JournalJ Clin Lipidol
PubMed ID28391912
PubMed Central IDPMC5407297
Grant ListUM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069423 / AI / NIAID NIH HHS / United States
UM1 AI069503 / AI / NIAID NIH HHS / United States
UM1 AI069501 / AI / NIAID NIH HHS / United States
UM1 AI069472 / AI / NIAID NIH HHS / United States
UL1 TR001111 / TR / NCATS NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069471 / AI / NIAID NIH HHS / United States
U01 AI069439 / AI / NIAID NIH HHS / United States
UM1 AI069534 / AI / NIAID NIH HHS / United States
UL1 TR000042 / TR / NCATS NIH HHS / United States
UM1 AI069439 / AI / NIAID NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UM1 AI069415 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States
UM1 AI069481 / AI / NIAID NIH HHS / United States
U01 AI069432 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069452 / AI / NIAID NIH HHS / United States
U01 AI069511 / AI / NIAID NIH HHS / United States
U01 AI069503 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1 AI069532 / AI / NIAID NIH HHS / United States
U01 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069419 / AI / NIAID NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
UM1 AI069511 / AI / NIAID NIH HHS / United States
U01 AI069494 / AI / NIAID NIH HHS / United States
P30 AI036219 / AI / NIAID NIH HHS / United States
U01 AI069471 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States