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

Clin Infect Dis. 2017 Jan 15;64(2):124-131. doi: 10.1093/cid/ciw683. Epub 2016 Oct 12.


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.

Keywords: acute HIV infection; antiretroviral therapy; inflammation; monocyte activation; sIL-6R.

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • Biomarkers
  • Blood Coagulation
  • CD4 Lymphocyte Count
  • Female
  • Fibrosis
  • Gastrointestinal Microbiome
  • HIV Infections / complications*
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / virology*
  • Humans
  • Inflammation / complications*
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Inflammation Mediators
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Male
  • Permeability
  • Viral Load
  • Young Adult


  • Biomarkers
  • Inflammation Mediators