Persistent, Albeit reduced, chronic inflammation in persons starting antiretroviral therapy in acute HIV infection

Irini Sereti, Shelly J. Krebs, Nittaya Phanuphak, James L. Fletcher, Bonnie Slike, Suteeraporn Pinyakorn, Robert J. O'Connell, Adam Rupert, Nicolas Chomont, Victor Valcour, Jerome H. Kim, Merlin L. Robb, Nelson L. Michael, Daniel C. Douek, Jintanat Ananworanich, Netanya S. Utay

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Background. Serious non-AIDS events cause substantial disease and death despite human immunodeficiency virus (HIV) suppression with antiretroviral therapy (ART). Biomarkers of inflammation, coagulation cascade activation, and fibrosis predict these end-organ events. We aimed to determine whether ART initiation during acute HIV infection would attenuate changes in these biomarker levels. Methods. Plasma samples were obtained from participants starting ART during acute or chronic HIV infection and from HIVuninfected participants from Bangkok, Thailand. Biomarkers of inflammation (C-reactive protein [CRP], interleukin 6, soluble interleukin 6 receptor [sIL-6R], soluble gp130, tumor necrosis factor [TNF]), enterocyte turnover (intestinal fatty acid binding protein [I-FABP]), lipopolysaccharide-induced monocyte activation (soluble CD14 [sCD14]), coagulation cascade activation [D-dimer], and fibrosis (hyaluronic acid [HA]) were measured at baseline and through 96 weeks of ART. Results. CRP, TNF, sIL-6R, I-FABP, sCD14, D-dimer, and HA levels were elevated in acute HIV infection. Early ART was associated with increased I-FABP levels but normalization of TNF, sIL-6R, and D-dimer levels. CRP, sCD14, and HA levels decreased during ART but remained elevated compared with HIV-uninfected participants. Higher sCD14, CRP, and D-dimer levels were associated with higher peripheral blood mononuclear cell and gut integrated HIV DNA levels. Decreases in sCD14 and CRP levels were correlated with increases in CD4 T-cell counts. Conclusions. ART initiated in early acute HIV infection was associated with normalization of the coagulation cascade and several systemic inflammatory biomarkers, but the acute-phase response, enterocyte turnover, monocyte activation, and fibrosis biomarkers remained elevated. Additional interventions to attenuate inflammation may be needed to optimize clinical outcomes in persons with HIV infection.

Original languageEnglish (US)
Pages (from-to)124-131
Number of pages8
JournalClinical Infectious Diseases
Volume64
Issue number2
DOIs
StatePublished - 2017

Fingerprint

Virus Diseases
HIV
Inflammation
C-Reactive Protein
Interleukin-6 Receptors
Biomarkers
Fatty Acid-Binding Proteins
Hyaluronic Acid
Fibrosis
Tumor Necrosis Factor-alpha
Enterocytes
Therapeutics
Monocytes
Cytokine Receptor gp130
Acute-Phase Reaction
Thailand
CD4 Lymphocyte Count
Secondary Prevention
Lipopolysaccharides
Interleukin-6

Keywords

  • Acute HIV infection
  • Antiretroviral therapy
  • Inflammation
  • Monocyte activation
  • Sil-6R

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

Cite this

Sereti, I., Krebs, S. J., Phanuphak, N., Fletcher, J. L., Slike, B., Pinyakorn, S., ... Utay, N. S. (2017). Persistent, Albeit reduced, chronic inflammation in persons starting antiretroviral therapy in acute HIV infection. Clinical Infectious Diseases, 64(2), 124-131. https://doi.org/10.1093/cid/ciw683

Persistent, Albeit reduced, chronic inflammation in persons starting antiretroviral therapy in acute HIV infection. / Sereti, Irini; Krebs, Shelly J.; Phanuphak, Nittaya; Fletcher, James L.; Slike, Bonnie; Pinyakorn, Suteeraporn; O'Connell, Robert J.; Rupert, Adam; Chomont, Nicolas; Valcour, Victor; Kim, Jerome H.; Robb, Merlin L.; Michael, Nelson L.; Douek, Daniel C.; Ananworanich, Jintanat; Utay, Netanya S.

In: Clinical Infectious Diseases, Vol. 64, No. 2, 2017, p. 124-131.

Research output: Contribution to journalArticle

Sereti, I, Krebs, SJ, Phanuphak, N, Fletcher, JL, Slike, B, Pinyakorn, S, O'Connell, RJ, Rupert, A, Chomont, N, Valcour, V, Kim, JH, Robb, ML, Michael, NL, Douek, DC, Ananworanich, J & Utay, NS 2017, 'Persistent, Albeit reduced, chronic inflammation in persons starting antiretroviral therapy in acute HIV infection', Clinical Infectious Diseases, vol. 64, no. 2, pp. 124-131. https://doi.org/10.1093/cid/ciw683
Sereti, Irini ; Krebs, Shelly J. ; Phanuphak, Nittaya ; Fletcher, James L. ; Slike, Bonnie ; Pinyakorn, Suteeraporn ; O'Connell, Robert J. ; Rupert, Adam ; Chomont, Nicolas ; Valcour, Victor ; Kim, Jerome H. ; Robb, Merlin L. ; Michael, Nelson L. ; Douek, Daniel C. ; Ananworanich, Jintanat ; Utay, Netanya S. / Persistent, Albeit reduced, chronic inflammation in persons starting antiretroviral therapy in acute HIV infection. In: Clinical Infectious Diseases. 2017 ; Vol. 64, No. 2. pp. 124-131.
@article{919a37083ada4dc4a8dc4feff42e6961,
title = "Persistent, Albeit reduced, chronic inflammation in persons starting antiretroviral therapy in acute HIV infection",
abstract = "Background. Serious non-AIDS events cause substantial disease and death despite human immunodeficiency virus (HIV) suppression with antiretroviral therapy (ART). Biomarkers of inflammation, coagulation cascade activation, and fibrosis predict these end-organ events. We aimed to determine whether ART initiation during acute HIV infection would attenuate changes in these biomarker levels. Methods. Plasma samples were obtained from participants starting ART during acute or chronic HIV infection and from HIVuninfected participants from Bangkok, Thailand. Biomarkers of inflammation (C-reactive protein [CRP], interleukin 6, soluble interleukin 6 receptor [sIL-6R], soluble gp130, tumor necrosis factor [TNF]), enterocyte turnover (intestinal fatty acid binding protein [I-FABP]), lipopolysaccharide-induced monocyte activation (soluble CD14 [sCD14]), coagulation cascade activation [D-dimer], and fibrosis (hyaluronic acid [HA]) were measured at baseline and through 96 weeks of ART. Results. CRP, TNF, sIL-6R, I-FABP, sCD14, D-dimer, and HA levels were elevated in acute HIV infection. Early ART was associated with increased I-FABP levels but normalization of TNF, sIL-6R, and D-dimer levels. CRP, sCD14, and HA levels decreased during ART but remained elevated compared with HIV-uninfected participants. Higher sCD14, CRP, and D-dimer levels were associated with higher peripheral blood mononuclear cell and gut integrated HIV DNA levels. Decreases in sCD14 and CRP levels were correlated with increases in CD4 T-cell counts. Conclusions. ART initiated in early acute HIV infection was associated with normalization of the coagulation cascade and several systemic inflammatory biomarkers, but the acute-phase response, enterocyte turnover, monocyte activation, and fibrosis biomarkers remained elevated. Additional interventions to attenuate inflammation may be needed to optimize clinical outcomes in persons with HIV infection.",
keywords = "Acute HIV infection, Antiretroviral therapy, Inflammation, Monocyte activation, Sil-6R",
author = "Irini Sereti and Krebs, {Shelly J.} and Nittaya Phanuphak and Fletcher, {James L.} and Bonnie Slike and Suteeraporn Pinyakorn and O'Connell, {Robert J.} and Adam Rupert and Nicolas Chomont and Victor Valcour and Kim, {Jerome H.} and Robb, {Merlin L.} and Michael, {Nelson L.} and Douek, {Daniel C.} and Jintanat Ananworanich and Utay, {Netanya S.}",
year = "2017",
doi = "10.1093/cid/ciw683",
language = "English (US)",
volume = "64",
pages = "124--131",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Persistent, Albeit reduced, chronic inflammation in persons starting antiretroviral therapy in acute HIV infection

AU - Sereti, Irini

AU - Krebs, Shelly J.

AU - Phanuphak, Nittaya

AU - Fletcher, James L.

AU - Slike, Bonnie

AU - Pinyakorn, Suteeraporn

AU - O'Connell, Robert J.

AU - Rupert, Adam

AU - Chomont, Nicolas

AU - Valcour, Victor

AU - Kim, Jerome H.

AU - Robb, Merlin L.

AU - Michael, Nelson L.

AU - Douek, Daniel C.

AU - Ananworanich, Jintanat

AU - Utay, Netanya S.

PY - 2017

Y1 - 2017

N2 - Background. Serious non-AIDS events cause substantial disease and death despite human immunodeficiency virus (HIV) suppression with antiretroviral therapy (ART). Biomarkers of inflammation, coagulation cascade activation, and fibrosis predict these end-organ events. We aimed to determine whether ART initiation during acute HIV infection would attenuate changes in these biomarker levels. Methods. Plasma samples were obtained from participants starting ART during acute or chronic HIV infection and from HIVuninfected participants from Bangkok, Thailand. Biomarkers of inflammation (C-reactive protein [CRP], interleukin 6, soluble interleukin 6 receptor [sIL-6R], soluble gp130, tumor necrosis factor [TNF]), enterocyte turnover (intestinal fatty acid binding protein [I-FABP]), lipopolysaccharide-induced monocyte activation (soluble CD14 [sCD14]), coagulation cascade activation [D-dimer], and fibrosis (hyaluronic acid [HA]) were measured at baseline and through 96 weeks of ART. Results. CRP, TNF, sIL-6R, I-FABP, sCD14, D-dimer, and HA levels were elevated in acute HIV infection. Early ART was associated with increased I-FABP levels but normalization of TNF, sIL-6R, and D-dimer levels. CRP, sCD14, and HA levels decreased during ART but remained elevated compared with HIV-uninfected participants. Higher sCD14, CRP, and D-dimer levels were associated with higher peripheral blood mononuclear cell and gut integrated HIV DNA levels. Decreases in sCD14 and CRP levels were correlated with increases in CD4 T-cell counts. Conclusions. ART initiated in early acute HIV infection was associated with normalization of the coagulation cascade and several systemic inflammatory biomarkers, but the acute-phase response, enterocyte turnover, monocyte activation, and fibrosis biomarkers remained elevated. Additional interventions to attenuate inflammation may be needed to optimize clinical outcomes in persons with HIV infection.

AB - Background. Serious non-AIDS events cause substantial disease and death despite human immunodeficiency virus (HIV) suppression with antiretroviral therapy (ART). Biomarkers of inflammation, coagulation cascade activation, and fibrosis predict these end-organ events. We aimed to determine whether ART initiation during acute HIV infection would attenuate changes in these biomarker levels. Methods. Plasma samples were obtained from participants starting ART during acute or chronic HIV infection and from HIVuninfected participants from Bangkok, Thailand. Biomarkers of inflammation (C-reactive protein [CRP], interleukin 6, soluble interleukin 6 receptor [sIL-6R], soluble gp130, tumor necrosis factor [TNF]), enterocyte turnover (intestinal fatty acid binding protein [I-FABP]), lipopolysaccharide-induced monocyte activation (soluble CD14 [sCD14]), coagulation cascade activation [D-dimer], and fibrosis (hyaluronic acid [HA]) were measured at baseline and through 96 weeks of ART. Results. CRP, TNF, sIL-6R, I-FABP, sCD14, D-dimer, and HA levels were elevated in acute HIV infection. Early ART was associated with increased I-FABP levels but normalization of TNF, sIL-6R, and D-dimer levels. CRP, sCD14, and HA levels decreased during ART but remained elevated compared with HIV-uninfected participants. Higher sCD14, CRP, and D-dimer levels were associated with higher peripheral blood mononuclear cell and gut integrated HIV DNA levels. Decreases in sCD14 and CRP levels were correlated with increases in CD4 T-cell counts. Conclusions. ART initiated in early acute HIV infection was associated with normalization of the coagulation cascade and several systemic inflammatory biomarkers, but the acute-phase response, enterocyte turnover, monocyte activation, and fibrosis biomarkers remained elevated. Additional interventions to attenuate inflammation may be needed to optimize clinical outcomes in persons with HIV infection.

KW - Acute HIV infection

KW - Antiretroviral therapy

KW - Inflammation

KW - Monocyte activation

KW - Sil-6R

UR - http://www.scopus.com/inward/record.url?scp=85015223658&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85015223658&partnerID=8YFLogxK

U2 - 10.1093/cid/ciw683

DO - 10.1093/cid/ciw683

M3 - Article

VL - 64

SP - 124

EP - 131

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 2

ER -