Intestinal Damage and Inflammatory Biomarkers in Human Immunodeficiency Virus (HIV)-Exposed and HIV-Infected Zimbabwean Infants

J Infect Dis. 2017 Sep 15;216(6):651-661. doi: 10.1093/infdis/jix367.

Abstract

Background: Disease progression is rapid in human immunodeficiency virus (HIV)-infected infants. Whether intestinal damage and inflammation underlie mortality is unknown.

Methods: We measured plasma intestinal fatty acid binding protein (I-FABP), soluble CD14 (sCD14), interleukin 6 (IL-6), and C-reactive protein (CRP) at 6 weeks and 6 months of age in 272 HIV-infected infants who either died (cases) or survived (controls), and in 194 HIV-exposed uninfected (HEU) and 197 HIV-unexposed infants. We estimated multivariable odds ratios for mortality and postnatal HIV transmission for each biomarker using logistic regression.

Results: At 6 weeks, HIV-infected infants had higher sCD14 and IL-6 but lower I-FABP than HIV-exposed and HIV-unexposed infants (P < .001). CRP was higher in HIV-exposed than HIV-unexposed infants (P = .02). At 6 months, HIV-infected infants had highest sCD14, IL-6, and CRP concentrations (P < .001) and marginally higher I-FABP than other groups (P = .07). CRP remained higher in HIV-exposed vs HIV-unexposed infants (P = .04). No biomarker was associated with mortality in HIV-infected infants, or with odds of breast-milk HIV transmission in HIV-exposed infants.

Conclusions: HIV-infected infants have elevated inflammatory markers by 6 weeks of age, which increase over time. In contrast to adults and older children, inflammatory biomarkers were not associated with mortality. HEU infants have higher inflammation than HIV-unexposed infants until at least 6 months, which may contribute to poor health outcomes.

Keywords: Africa; HIV; infant; inflammation; intestinal; mortality.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers / blood*
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Fatty Acid-Binding Proteins / blood
  • Female
  • HIV / isolation & purification
  • HIV / metabolism
  • HIV Infections / blood*
  • HIV Infections / diagnosis
  • Humans
  • Infant
  • Inflammation / blood
  • Inflammation / virology
  • Interleukin-6 / blood
  • Intestines / pathology*
  • Intestines / virology*
  • Lipopolysaccharide Receptors / blood
  • Male
  • Multivariate Analysis
  • Randomized Controlled Trials as Topic
  • Sample Size
  • Zimbabwe / epidemiology

Substances

  • Biomarkers
  • FABP2 protein, human
  • Fatty Acid-Binding Proteins
  • IL6 protein, human
  • Interleukin-6
  • Lipopolysaccharide Receptors
  • C-Reactive Protein