Sahera Dirajlal-Fargo1,2,3, Marisa M Mussi-Pinhata4, Adriana Weinberg5, Qilu Yu6, Rachel Cohen6, D Robert Harris6, Emily Bowman7, Janelle Gabriel7, Manjusha Kulkarni7, Nicholas Funderburg7, Nahida Chakhtoura8, Grace A McComsey1,2,3. 1. University Hospitals Cleveland Medical Center. 2. Rainbow Babies and Children's Hospital. 3. Case Western Reserve University, Department of Pediatrics, Cleveland, Ohio, USA. 4. Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil. 5. Anschutz Medical Center, University of Colorado Division of Infectious Diseases, Denver, Colorado. 6. WESTAT, Rockville, Maryland. 7. Ohio State University School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Columbus, Ohio. 8. Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, USA.
Abstract
BACKGROUND: HIV-exposed-uninfected (HEU) infants have increased infectious morbidity and mortality; little is known about their levels of inflammation and monocyte activation. METHODS: Plasma samples obtained at birth and 6 months from 86 HEU mother-infant pairs enrolled in the National Institute of Child Health and Human Development cohorts in Brazil were compared with 88 HIV-unexposed mother-infant pairs. HIV-infected mothers received antiretroviral therapy during pregnancy, their infants received zidovudine prophylaxis and were not breastfed. IL-6, soluble TNFα receptor I (sTNF-RI) and II, soluble CD14, soluble CD163, IFN-γ-induced protein 10 (IP-10), vascular cell adhesion molecule, oxidized LDL, D-dimer and high-sensitivity C-reactive protein were assayed by ELISA at birth and at 6 months. sTNF-RI and IL-6 were considered coprimary endpoints. RESULTS: Among HIV-infected mothers, 79% had HIV-RNA less than 400 copies/ml prior to delivery. Compared with HIV-unexposed, HEU infants had a lower mean gestational age (38.7 vs. 39.3 weeks) and weight (3.1 vs. 3.3 kg); and reached lower weight (5.9 vs. 8.5 kg) and height (53.6 vs. 68.8 cm) at 6 months. With the exception of vascular cell adhesion molecule, inflammatory markers were generally higher (P ≤ 0.005) in HEU at birth, but at 6 months only sTNF-RI and IL-6 remained higher. For HEU pairs, only IP-10 was associated with maternal levels at birth (P < 0.001). In HEU, elevated levels of high-sensitivity C-reactive protein and IP-10 at birth were associated with lower weight at birth (P = 0.04) and at 6 months (P = 0.04). CONCLUSION: HIV-exposed infants have heightened inflammation and monocyte activation at birth, which for some markers persisted to 6 months of life and was not related to maternal inflammatory status. Inflammation may contribute to the increased HEU infectious morbidity and poor growth.
BACKGROUND:HIV-exposed-uninfected (HEU) infants have increased infectious morbidity and mortality; little is known about their levels of inflammation and monocyte activation. METHODS: Plasma samples obtained at birth and 6 months from 86 HEU mother-infant pairs enrolled in the National Institute of Child Health and Human Development cohorts in Brazil were compared with 88 HIV-unexposed mother-infant pairs. HIV-infected mothers received antiretroviral therapy during pregnancy, their infants received zidovudine prophylaxis and were not breastfed. IL-6, soluble TNFα receptor I (sTNF-RI) and II, soluble CD14, soluble CD163, IFN-γ-induced protein 10 (IP-10), vascular cell adhesion molecule, oxidized LDL, D-dimer and high-sensitivity C-reactive protein were assayed by ELISA at birth and at 6 months. sTNF-RI and IL-6 were considered coprimary endpoints. RESULTS: Among HIV-infected mothers, 79% had HIV-RNA less than 400 copies/ml prior to delivery. Compared with HIV-unexposed, HEU infants had a lower mean gestational age (38.7 vs. 39.3 weeks) and weight (3.1 vs. 3.3 kg); and reached lower weight (5.9 vs. 8.5 kg) and height (53.6 vs. 68.8 cm) at 6 months. With the exception of vascular cell adhesion molecule, inflammatory markers were generally higher (P ≤ 0.005) in HEU at birth, but at 6 months only sTNF-RI and IL-6 remained higher. For HEU pairs, only IP-10 was associated with maternal levels at birth (P < 0.001). In HEU, elevated levels of high-sensitivity C-reactive protein and IP-10 at birth were associated with lower weight at birth (P = 0.04) and at 6 months (P = 0.04). CONCLUSION:HIV-exposed infants have heightened inflammation and monocyte activation at birth, which for some markers persisted to 6 months of life and was not related to maternal inflammatory status. Inflammation may contribute to the increased HEU infectious morbidity and poor growth.
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