HIV replication, inflammation, and the effect of starting antiretroviral therapy on plasma asymmetric dimethylarginine, a novel marker of endothelial dysfunction

Jason V. Baker, Jacqueline Neuhaus, Daniel Duprez, Matthew Freiberg, Jose I. Bernardino, Andrew David Badley, Daniel E. Nixon, Jens D. Lundgren, Russell P. Tracy, James D. Neaton

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: HIV infection is associated with premature development of cardiovascular disease. Understanding the effects of HIV replication on endothelial dysfunction and platelet activation may identify treatment targets to reduce cardiovascular disease risk. Methods: A subgroup of HIV-infected participants in the Strategies for Management of Antiretroviral Therapy study off antiretroviral therapy (ART) at entry enabled a randomized comparison of immediate versus deferred ART initiation of changes in asymmetric dimethylarginine (ADMA), soluble CD40 ligand (sCD40L), and P-selectin levels. Results: At study entry, median (interquartile range) levels of ADMA, sCD40L, and P-selectin were 0.57 (0.49-0.66) μg/mL, 251 (135-696) μmol/L, and 34 (28-44) pg/mL. Compared to those randomized to deferral of ART (n = 114), participants randomized to immediate ART (n = 134) had 10.3% lower ADMA levels (P = 0.003) at 12 months; treatment differences in sCD40L (95% confidence interval: 217% to 44%; P = 0.53) and P-selectin (95% confidence interval: 210% to 10%; P = 0.95) were not significant. The difference in ADMA for those assigned immediate ART compared with those assigned ART deferral was greater among younger patients and those with higher levels of high-sensitivity C-reactive protein and D-dimer (P ≤ 0.05 for interaction for both) but not HIV RNA level at baseline (P = 0.51). Discussion: ART initiation leads to declines in ADMA levels, a marker of nitric oxide-mediated endothelial dysfunction. Improvement in ADMA levels was related to the degree of inflammation and coagulation, suggesting that upregulation of these pathways contributes to premature vascular disease among individuals with HIV infection. Whether declines in ADMA levels impact risk of disease requires further research.

Original languageEnglish (US)
Pages (from-to)128-134
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume60
Issue number2
DOIs
StatePublished - Jun 1 2012

Fingerprint

HIV
Inflammation
CD40 Ligand
P-Selectin
Therapeutics
HIV Infections
Cardiovascular Diseases
N,N-dimethylarginine
Confidence Intervals
Platelet Activation
Vascular Diseases
C-Reactive Protein
Nitric Oxide
Up-Regulation
RNA
Research

Keywords

  • Antiretroviral therapy
  • Asymmetric dimethylarginine (ADMA)
  • CD40 ligand
  • Endothelial dysfunction
  • HIV infection
  • Inflammation
  • P-selectin

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

HIV replication, inflammation, and the effect of starting antiretroviral therapy on plasma asymmetric dimethylarginine, a novel marker of endothelial dysfunction. / Baker, Jason V.; Neuhaus, Jacqueline; Duprez, Daniel; Freiberg, Matthew; Bernardino, Jose I.; Badley, Andrew David; Nixon, Daniel E.; Lundgren, Jens D.; Tracy, Russell P.; Neaton, James D.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 60, No. 2, 01.06.2012, p. 128-134.

Research output: Contribution to journalArticle

Baker, Jason V. ; Neuhaus, Jacqueline ; Duprez, Daniel ; Freiberg, Matthew ; Bernardino, Jose I. ; Badley, Andrew David ; Nixon, Daniel E. ; Lundgren, Jens D. ; Tracy, Russell P. ; Neaton, James D. / HIV replication, inflammation, and the effect of starting antiretroviral therapy on plasma asymmetric dimethylarginine, a novel marker of endothelial dysfunction. In: Journal of Acquired Immune Deficiency Syndromes. 2012 ; Vol. 60, No. 2. pp. 128-134.
@article{83a0d741761441c09ca515f26f52d3d0,
title = "HIV replication, inflammation, and the effect of starting antiretroviral therapy on plasma asymmetric dimethylarginine, a novel marker of endothelial dysfunction",
abstract = "Background: HIV infection is associated with premature development of cardiovascular disease. Understanding the effects of HIV replication on endothelial dysfunction and platelet activation may identify treatment targets to reduce cardiovascular disease risk. Methods: A subgroup of HIV-infected participants in the Strategies for Management of Antiretroviral Therapy study off antiretroviral therapy (ART) at entry enabled a randomized comparison of immediate versus deferred ART initiation of changes in asymmetric dimethylarginine (ADMA), soluble CD40 ligand (sCD40L), and P-selectin levels. Results: At study entry, median (interquartile range) levels of ADMA, sCD40L, and P-selectin were 0.57 (0.49-0.66) μg/mL, 251 (135-696) μmol/L, and 34 (28-44) pg/mL. Compared to those randomized to deferral of ART (n = 114), participants randomized to immediate ART (n = 134) had 10.3{\%} lower ADMA levels (P = 0.003) at 12 months; treatment differences in sCD40L (95{\%} confidence interval: 217{\%} to 44{\%}; P = 0.53) and P-selectin (95{\%} confidence interval: 210{\%} to 10{\%}; P = 0.95) were not significant. The difference in ADMA for those assigned immediate ART compared with those assigned ART deferral was greater among younger patients and those with higher levels of high-sensitivity C-reactive protein and D-dimer (P ≤ 0.05 for interaction for both) but not HIV RNA level at baseline (P = 0.51). Discussion: ART initiation leads to declines in ADMA levels, a marker of nitric oxide-mediated endothelial dysfunction. Improvement in ADMA levels was related to the degree of inflammation and coagulation, suggesting that upregulation of these pathways contributes to premature vascular disease among individuals with HIV infection. Whether declines in ADMA levels impact risk of disease requires further research.",
keywords = "Antiretroviral therapy, Asymmetric dimethylarginine (ADMA), CD40 ligand, Endothelial dysfunction, HIV infection, Inflammation, P-selectin",
author = "Baker, {Jason V.} and Jacqueline Neuhaus and Daniel Duprez and Matthew Freiberg and Bernardino, {Jose I.} and Badley, {Andrew David} and Nixon, {Daniel E.} and Lundgren, {Jens D.} and Tracy, {Russell P.} and Neaton, {James D.}",
year = "2012",
month = "6",
day = "1",
doi = "10.1097/QAI.0b013e318252f99f",
language = "English (US)",
volume = "60",
pages = "128--134",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - HIV replication, inflammation, and the effect of starting antiretroviral therapy on plasma asymmetric dimethylarginine, a novel marker of endothelial dysfunction

AU - Baker, Jason V.

AU - Neuhaus, Jacqueline

AU - Duprez, Daniel

AU - Freiberg, Matthew

AU - Bernardino, Jose I.

AU - Badley, Andrew David

AU - Nixon, Daniel E.

AU - Lundgren, Jens D.

AU - Tracy, Russell P.

AU - Neaton, James D.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Background: HIV infection is associated with premature development of cardiovascular disease. Understanding the effects of HIV replication on endothelial dysfunction and platelet activation may identify treatment targets to reduce cardiovascular disease risk. Methods: A subgroup of HIV-infected participants in the Strategies for Management of Antiretroviral Therapy study off antiretroviral therapy (ART) at entry enabled a randomized comparison of immediate versus deferred ART initiation of changes in asymmetric dimethylarginine (ADMA), soluble CD40 ligand (sCD40L), and P-selectin levels. Results: At study entry, median (interquartile range) levels of ADMA, sCD40L, and P-selectin were 0.57 (0.49-0.66) μg/mL, 251 (135-696) μmol/L, and 34 (28-44) pg/mL. Compared to those randomized to deferral of ART (n = 114), participants randomized to immediate ART (n = 134) had 10.3% lower ADMA levels (P = 0.003) at 12 months; treatment differences in sCD40L (95% confidence interval: 217% to 44%; P = 0.53) and P-selectin (95% confidence interval: 210% to 10%; P = 0.95) were not significant. The difference in ADMA for those assigned immediate ART compared with those assigned ART deferral was greater among younger patients and those with higher levels of high-sensitivity C-reactive protein and D-dimer (P ≤ 0.05 for interaction for both) but not HIV RNA level at baseline (P = 0.51). Discussion: ART initiation leads to declines in ADMA levels, a marker of nitric oxide-mediated endothelial dysfunction. Improvement in ADMA levels was related to the degree of inflammation and coagulation, suggesting that upregulation of these pathways contributes to premature vascular disease among individuals with HIV infection. Whether declines in ADMA levels impact risk of disease requires further research.

AB - Background: HIV infection is associated with premature development of cardiovascular disease. Understanding the effects of HIV replication on endothelial dysfunction and platelet activation may identify treatment targets to reduce cardiovascular disease risk. Methods: A subgroup of HIV-infected participants in the Strategies for Management of Antiretroviral Therapy study off antiretroviral therapy (ART) at entry enabled a randomized comparison of immediate versus deferred ART initiation of changes in asymmetric dimethylarginine (ADMA), soluble CD40 ligand (sCD40L), and P-selectin levels. Results: At study entry, median (interquartile range) levels of ADMA, sCD40L, and P-selectin were 0.57 (0.49-0.66) μg/mL, 251 (135-696) μmol/L, and 34 (28-44) pg/mL. Compared to those randomized to deferral of ART (n = 114), participants randomized to immediate ART (n = 134) had 10.3% lower ADMA levels (P = 0.003) at 12 months; treatment differences in sCD40L (95% confidence interval: 217% to 44%; P = 0.53) and P-selectin (95% confidence interval: 210% to 10%; P = 0.95) were not significant. The difference in ADMA for those assigned immediate ART compared with those assigned ART deferral was greater among younger patients and those with higher levels of high-sensitivity C-reactive protein and D-dimer (P ≤ 0.05 for interaction for both) but not HIV RNA level at baseline (P = 0.51). Discussion: ART initiation leads to declines in ADMA levels, a marker of nitric oxide-mediated endothelial dysfunction. Improvement in ADMA levels was related to the degree of inflammation and coagulation, suggesting that upregulation of these pathways contributes to premature vascular disease among individuals with HIV infection. Whether declines in ADMA levels impact risk of disease requires further research.

KW - Antiretroviral therapy

KW - Asymmetric dimethylarginine (ADMA)

KW - CD40 ligand

KW - Endothelial dysfunction

KW - HIV infection

KW - Inflammation

KW - P-selectin

UR - http://www.scopus.com/inward/record.url?scp=84862155139&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862155139&partnerID=8YFLogxK

U2 - 10.1097/QAI.0b013e318252f99f

DO - 10.1097/QAI.0b013e318252f99f

M3 - Article

C2 - 22421746

AN - SCOPUS:84862155139

VL - 60

SP - 128

EP - 134

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 2

ER -