Increased Metabolic Activity on 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Human Immunodeficiency Virus-Associated Immune Reconstitution Inflammatory Syndrome

Clin Infect Dis. 2019 Jan 7;68(2):229-238. doi: 10.1093/cid/ciy454.

Abstract

Background: Immune reconstitution inflammatory syndrome (IRIS) represents an unexpected inflammatory response shortly after initiation of antiretroviral therapy (ART) in some human immunodeficiency virus (HIV)-infected patients with underlying neoplasia or opportunistic infections, including tuberculosis. We hypothesized that IRIS is associated with increased glycolysis and that 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) could help identify high-risk subjects.

Methods: In this prospective cohort study, 30 HIV-infected patients (CD4+ count <100 cells/µL) underwent FDG-PET/CT scans at baseline and 4-8 weeks after ART initiation. Ten patients developed IRIS (6 mycobacterial).

Results: At baseline, total glycolytic activity, total lesion volume, and maximum standardized uptake values (SUVs) of pathologic FDG uptake (reflective of opportunistic disease burden) were significantly higher in IRIS vs non-IRIS (P = .010, .017, and .029, respectively) and significantly correlated with soluble inflammatory biomarkers (interferon-γ, myeloperoxidase, tumor necrosis factor, interleukin 6, soluble CD14). Baseline bone marrow (BM) and spleen FDG uptake was higher in mycobacterial IRIS specifically. After ART initiation, BM and spleen mean SUV decreased in non-IRIS (P = .004, .013) but not IRIS subjects. Our results were supported by significantly higher glucose transporter 1 (Glut-1) expression of CD4+ cells and monocytes after ART initiation in IRIS/mycobacterial IRIS compared with non-IRIS patients.

Conclusions: We conclude that increased pathologic metabolic activity on FDG-PET/CT prior to ART initiation is associated with IRIS development and correlates with inflammatory biomarkers. Abnormally elevated BM and spleen metabolism is associated with mycobacterial IRIS, HIV viremia, and Glut-1 expression on CD4+ cells and monocytes.

Clinical trials registration: NCT02147405.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Biomarkers
  • Female
  • Fluorodeoxyglucose F18*
  • Gene Expression Regulation / drug effects
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • HIV Infections / complications*
  • Humans
  • Immune Reconstitution Inflammatory Syndrome / diagnostic imaging*
  • Immune Reconstitution Inflammatory Syndrome / metabolism*
  • Male
  • Monocytes / metabolism
  • Positron Emission Tomography Computed Tomography*
  • Radiopharmaceuticals / pharmacology
  • T-Lymphocytes / metabolism

Substances

  • Anti-HIV Agents
  • Biomarkers
  • Glucose Transporter Type 1
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18

Associated data

  • ClinicalTrials.gov/NCT02147405