Factors Associated with Lower Respiratory Tract Infections in HIV-Exposed Uninfected Infants.

To identify factors that predispose human immunodeficiency virus (HIV)-exposed uninfected infants (HEUs) to higher incidence of severe infections, hospitalization, and death in the first 6-24 months of life compared with HEUs with and without lower respiratory tract infection (LRTI) in the first 6 months of life. Nested case-control study of 107 LRTI+ infants enrolled in the International Site Development Initiative (NISDI) Perinatal and Longitudinal Study in Latin American Countries (LILAC) studies with and 140 LRTI- in the first 6 months, matched by date and place of birth. Infants and mothers had plasma antibodies measured against respiratory syncytial virus (RSV), parainfluenza (PIV) 1, 2, 3, influenza, and pneumococcus 1, 5, 6B, and 14. Compared with LRTI-, mothers of LRTI+ HEUs had lower years of education, lower CD4+ cells, and higher HIV plasma viral load at delivery, but similar use of antiretrovirals and cotrimoxazole and other sociodemographic characteristics. LRTI+ and LRTI- HEUs had similar demographic and hematological characteristics and antibody concentrations against respiratory pathogens at birth. At 6 months, the rates of seroconversions to respiratory pathogens and antibody responses to tetanus vaccine were also similar. However, antibody concentrations to RSV were significantly higher in LRTI+ compared with LRTI- HEUs and marginally higher to PIV1. Maternal factors associated with advanced HIV disease, but unrelated to the use of antiretrovirals, cotrimoxazole, or the level of maternal antibodies against respiratory pathogens, contribute to the increased risk of LRTI in HEUs. In HEUs, antiretroviral and cotrimoxazole use, exposure to respiratory pathogens and humoral immune responses were not associated with the incidence of LRTI.

Excess respiratory viral infections and low antibody responses among HIV-exposed, uninfected infants.

OBJECTIVE: HIV-exposed uninfected (HEUs) infants have frequent severe infection, hospitalization, and death. We performed a serologic investigation to determine the role of common childhood respiratory pathogens in the excess incidence of infections in HEUs. DESIGN: Prospective cohort study of mother-infant pairs. METHODS: Among 247 HEUs and 88 HIV-unexposed uninfected (HUU) infant-mother pairs, we measured maternal antibodies to respiratory syncytial virus (RSV) and pneumococcus (PNC 1, 5, 6B, 14); infant antibodies to RSV, influenza A (flu), parainfluenza viruses (1, 2, 3), and PNC 1, 5, 6B, and 14 were measured at 0 and 6 months, and antitetanus antibodies at 6 months. RESULTS: HIV-infected mothers had higher RSV and lower PNC antibody concentrations at delivery than uninfected mothers. Transplacental transfer of maternal antibodies, particularly for RSV, was lower in HEUs compared with HUUs. At birth, HEUs had higher concentrations of anti-RSV antibodies than HUUs, but lower antibodies to the other respiratory agents. At 6 months, HEUs had significantly higher proportions of seroconversions and higher antibody concentrations against parainfluenza viruses 1, 2, and 3. There were no significant differences in seroconversions to flu and RSV, but antibody concentrations to RSV were six-fold lower in HEUs versus HUUs at 6 months. Antibody responses to at least two doses of tetanus vaccine were also six-fold lower in HEUs compared with HUUs. CONCLUSION: Six-month-old HEUs had a higher incidence of respiratory viral infections than HUUs. In addition to the low passive protection from maternal antibodies, low antibody responses of HEUs may contribute to increased morbidity and mortality.