4.7 Article

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

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 216, Issue 6, Pages 651-661

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jix367

Keywords

HIV; infant; Africa; inflammation; mortality; intestinal

Funding

  1. Wellcome Trust [093768/Z/10/Z]
  2. Canadian International Development Agency (R/C Project) [690/M3688]
  3. US Agency for International Development (USAID) [HRN-A-00-97-00015-00]
  4. Bill & Melinda Gates Foundation (Seattle, Washington)
  5. SARA Project
  6. USAID's Bureau for Africa, Office of Sustainable Development [AOT-C-00-99-00237-00]
  7. Rockefeller Foundation (New York, New York)
  8. BASF (Ludwigshafen, Germany)

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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.

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