Immunological abnormalities among HIV-exposed uninfected infants of immunologically suppressed mothers
Background: Recent reports of increased morbidity and mortality from infectious diseases among HIV-exposed uninfected (HEU) infants have raised concern about possible immune dysfunction among them. The objective of this study was to assess the association between maternal viremia and CD4+ T cell count at the time of delivery and the developing immune system of their infants.
Methods: The Centre maternel et infantile sur le sida (CMIS) mother-child cohort was established in 1987 to follow HIV infected mothers and their infants. CD4, CD8, CD19% and absolute neutrophil counts were compared at 2, 6 and 12 months of age among 585 infants born to mothers with different levels of CD4+ T cells and viremia at delivery. The association between maternal factors and infant immune parameters were then assessed by multivariate linear regression.
Results: Median absolute CD4+ T cell counts (cells/mm³) at 2 and 6 months of age were significantly lower in HEU infants born to mothers with CD4 < 350 (n=139), compared to those with CD4 >350 (n=330), and again among those with delivery viral load >1000 copies/ml (n=45) compared to those with viral load < 1000 copies/ml (n=398).There were no significant differences in CD8+ T cell or absolute neutrophil count between groups.
| Infant Age | Maternal CD4 <350 | Maternal CD4 >350 | P | Maternal Viral Load >1000 | Maternal Viral Load <1000 | P |
| 2 months | 2480 (1960-3068) | 2660 (2079-3444) | 0.03 | 2419 (1936-2832) | 2695 (2091-3422) | 0.06 |
| 6 months | 2376 (1760-3283) | 2655 (2000-3432) | 0.05 | 2539 (1754-2917) | 2655 (2021-3599) | 0.04 |
| 12 months | 2013 (1238-2733) | 2184 (1568-2705) | 0.11 | 2064 (1728-2842) | 2184 (1559-2766) | 0.36 |
Maternal CD4 was the most significant factor associated with infant CD4 at two and 6 months of age on univariate analysis (p < 0.01, B coefficient=0.56), and remained a significant predictor of infant CD4 at two months of age after adjusting for maternal antiretroviral use, infant antiretroviral use, gestational age and gender (P< 0.01, B coefficient=0.51).
Conclusions: There were significant differences in absolute CD4+ T cell counts among HEU infants born to mothers with lower CD4 and higher viral load at delivery. Further work should be targeted towards understanding immune function among this subset of HEU infants.
F. Kakkar1, H. Soudeyns2,3, V. Lamarre1, B. Marc2,4, N. Lapointe1,3, CMIS Cohort Team
1University of Montreal, CHU Sainte-Justine, Infectious Diseases, Montreal, Canada, 2University of Montreal, Faculty of Medicine, Montreal, Canada, 3CHU Sainte Justine, Centre de Recherche, Montreal, Canada, 4University of Montreal, Obstetrics and Gynecology, Montreal, Canada