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.
N1 - Funding Information:
This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases; by a cooperative agreement (W81XWH- 11-2-0174) between The Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of Defense; and by the National Institutes of Health (grants R01MH095613 and R01NS061696 to SEARCH 010 and SEARCH 011, respectively). The Government Pharmaceutical Organization (GPO), Thailand, Gilead, Merck and ViiV Healthcare provided support for antiretroviral medications.
PY - 2017/1/15
Y1 - 2017/1/15
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
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U2 - 10.1093/cid/ciw683
DO - 10.1093/cid/ciw683
M3 - Article
AN - SCOPUS:85015223658
SN - 1058-4838
VL - 64
SP - 124
EP - 131
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 2
ER -