HIV infection is accompanied by high levels of inflammation that predict increased mortality in adults. HIV-exposed uninfected (HEU) infants also have increased infectious morbidity and mortality, but little is known about their levels of inflammation and immune activation. In this study, we assessed how inflammatory and monocyte activation markers correlated between mothers and HEUs at delivery and compared markers between HEU and HIV-unexposed (HU) infants at birth and at 6 months of life.
The study enrolled term singletons ≥2500g at birth and their mothers. Samples obtained at birth and 6 months from 86 HEU mother-infant pairs enrolled in the NICHD cohorts in Brazil were analyzed and compared to 88 HU mother-infant pairs. All HIV-infected mothers received ARV during pregnancy. HEUs received neonatal zidovudine prophylaxis and formula. HUs were born to healthy mothers, and most received formula feeding by 4 weeks of age. Infants had clinical and laboratory evaluations at birth and 6 months. IL-6, TNFRI, TNFRII, sCD14, sCD163, IP-10, VCAM, OxLDL, D Dimer, and hsCRP were assayed by ELISA. Data were analyzed using two-sample t-tests, correlation coefficients and linear regression models. p<0.005 was used to adjust for multiple comparisons.
Among HIV-infected mothers, 81.4% had HIV-RNA <1,000 copies/mL prior to delivery. In addition, they were older (27 vs. 24 years), and more frequently non-white (64.4% vs. 25.0%) when compared to uninfected mothers. Compared to HU, HEU infants were born more frequently by C-section (59% vs. 32%), with a lower median gestational age (38.6 vs. 39.3wk) and weight (3.2 vs. 3.3kg); and reached lower weight (5.9 vs. 8.5kg) and height (53.5 vs. 68.8 cm) at 6 months of age. Majority of inflammatory markers were significantly higher (p≤0.005) in HEU compared with HU at birth, but at 6 months only TNFRI and IL-6 remained higher (Table). Among HU mother-infant pairs, infant IL-6, TNFRI, TNFRII, sCD14, sCD163 levels at birth were associated with maternal levels at delivery (r≥0.31; p≤0.0004). For HEU pairs, the only association was for IP-10 (r=0.34; p<0.0001) at birth.
HEU infants had higher inflammation and monocyte activation than HU at birth, which for some markers persisted to 6 months of life, and was related to maternal inflammatory status. Inflammation may contribute to the increased HEU infectious morbidity and poor growth. This hypothesis warrants further investigation.