Persistent, Albeit Reduced, Chronic Inflammation in Persons Starting Antiretroviral Therapy in Acute HIV Infection

• Published in: Clinical infectious diseases Vol. 64; no. 2; pp. 124 - 131
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.01.2017
• Series: Editor's choice
• Subjects: Adult; Antiretroviral drugs; Antiretroviral Therapy, Highly Active; ARTICLES AND COMMENTARIES; Biomarkers; Blood Coagulation; CD4 Lymphocyte Count; Coagulation; Drug therapy; Female; Fibrosis; Gastrointestinal Microbiome; HIV; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; Human immunodeficiency virus; Humans; Inflammation; Inflammation - complications; Inflammation - metabolism; Inflammation - pathology; Inflammation Mediators; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Lentivirus; Major; Male; Permeability; Retroviridae; Viral Load; Young Adult; Thailand, Chacoengsao Prov., Bangkok; acute HIV infection; monocyte activation; inflammation; antiretroviral therapy; sIL-6R
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciw683

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 HIV-uninfected 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.