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 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.
authors.affiliation: Laboratory of Immunoregulation.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.|US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
authors.forename: Shelly J
authors.initials: SJ
authors.lastname: Krebs
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Center.
authors.forename: Nittaya
authors.initials: N
authors.lastname: Phanuphak
authors.affiliation: SEARCH, Thai Red Cross AIDS Research Center.
authors.forename: James L
authors.initials: JL
authors.lastname: Fletcher
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.|US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
authors.forename: Bonnie
authors.initials: B
authors.lastname: Slike
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.|US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
authors.forename: Suteeraporn
authors.initials: S
authors.lastname: Pinyakorn
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.|US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.|Department of Retrovirology, Armed Forces Research Institute of Medical Sciences, US Army Medical Component, Bangkok, Thailand.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.affiliation: AIDS Monitoring Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Maryland.
authors.forename: Adam
authors.initials: A
authors.lastname: Rupert
authors.affiliation: Centre de Recherche du CHUM and Department of Microbiology, Infectiology and Immunology, Université de Montréal, Quebec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.affiliation: Department of Neurology, University of California San Francisco Memory and Aging Center, Sandler Neurosciences Center.
authors.forename: Victor
authors.initials: V
authors.lastname: Valcour
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.|US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.|US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.|US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Douek
authors.affiliation: The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda.|US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring.|SEARCH, Thai Red Cross AIDS Research Center.
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch at Galveston neutay@utmb.edu.
authors.forename: Netanya S
authors.initials: NS
authors.lastname: Utay
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D001777:Blood Coagulation; D018791:CD4 Lymphocyte Count; D005260:Female; D005355:Fibrosis; D000069196:Gastrointestinal Microbiome; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators; D007413:Intestinal Mucosa / Q000378:metabolism / Q000382:microbiology; D008297:Male; D010539:Permeability; D019562:Viral Load; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators
keywords: acute HIV infection; antiretroviral therapy; inflammation; monocyte activation; sIL-6R