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Initiation of antiretroviral therapy in early HIV infection reduces but does not abrogate chronic residual inflammation.

Initiation of antiretroviral therapy in early HIV infection reduces but does not abrogate chronic residual inflammation.
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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, ,


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, , (click to view)

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, ,

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Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2016 Oct 12() pii

Abstract
BACKGROUND
 Serious non-AIDS events cause substantial morbidity and mortality despite 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 HIV infection, chronic HIV infection, and HIV-uninfected participants, from Bangkok, Thailand. Biomarkers of inflammation (C-reactive protein [CRP], interleukin 6 [IL-6], soluble IL-6 receptor [sIL-6R], soluble gp130 [sgp130], 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 to 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 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 people with HIV infection.

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