In Utero Infection with HIV-1 Associated with Suppressed Lymphoproliferative Responses at Birth.

Abstract

In utero exposure to HIV-1 may affect the immune system of the developing child and may induce HIV-1-specific immune responses, even in the absence of HIV-1 infection. We evaluated lymphoproliferative capacity at birth among 40 HIV-1-uninfected infants born to HIV-1-infected mothers and 10 infants who had acquired HIV-1 in utero. Cord blood mononuclear cells were assayed using 3 H-Thymidine incorporation for proliferation in response to HIV-1 p55-gag and the control stimuli phytohemagglutinin (PHA), Staphylococcus enterotoxin B (SEB), and allogeneic cells. In response to HIV-1 p55-gag, 8 (20%) of HIV-1-exposed, uninfected (EU) infants had a stimulation index (SI) ≥2 and 3 (30%) of in utero HIV-1 infected infants had SI ≥2. Frequency and magnitude of responses to HIV-1 p55-gag were low overall and did not differ statistically between groups. However, proliferative responses to control stimuli were significantly higher in EU infants than in infants infected in utero, with a median SI in response to PHA of 123 (Interquartile range [IQR] 77-231) versus 18 (IQR 4-86) between EU and infected infants, respectively (p<0.001). Among infected infants, gestational maturity was associated with the strength of HIV-1 p55-gag response (p<0.001); neither maternal nor infant HIV-1 viral load was associated. In summary, EU and HIV-1-infected infants mounted HIV-1-specific lymphoproliferative responses at similar rates (20-30%) and although global immune function was preserved among EU infants, neonatal immune responses were significantly compromised by HIV-1 infection. Such early lymphoproliferative compromise may in part explain rapid progression to AIDS and death among HIV-1-infected infants.

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