Longitudinal Assessment of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon Responses during the First Year of Life in HIV-1-Infected Infants
Lohman BL., Slyker JA., Richardson BA., Farquhar C., Mabuka JM., Crudder C., Dong T., Obimbo E., Mbori-Ngacha D., Overbaugh J., Rowland-Jones S., John-Stewart G.
<jats:title>ABSTRACT</jats:title> <jats:p>Human immunodeficiency virus type 1 (HIV-1) infection results in different patterns of viral replication in pediatric compared to adult populations. The role of early HIV-1-specific responses in viral control has not been well defined, because most studies of HIV-1-infected infants have been retrospective or cross-sectional. We evaluated the association between HIV-1-specific gamma interferon (IFN-γ) release from the cells of infants of 1 to 3 months of age and peak viral loads and mortality in the first year of life among 61 Kenyan HIV-1-infected infants. At 1 month, responses were detected in 7/12 (58%) and 6/21 (29%) of infants infected in utero and peripartum, respectively (<jats:italic>P</jats:italic> = 0.09), and in ∼50% of infants thereafter. Peaks of HIV-specific spot-forming units (SFU) increased significantly with age in all infants, from 251/10<jats:sup>6</jats:sup> peripheral blood mononuclear cells (PBMC) at 1 month of age to 501/10<jats:sup>6</jats:sup> PBMC at 12 months of age (<jats:italic>P</jats:italic> = 0.03), although when limited to infants who survived to 1 year, the increase in peak HIV-specific SFU was no longer significant (<jats:italic>P</jats:italic> = 0.18). Over the first year of life, infants with IFN-γ responses at 1 month had peak plasma viral loads, rates of decline of viral load, and mortality risk similar to those of infants who lacked responses at 1 month. The strength and breadth of IFN-γ responses at 1 month were not significantly associated with viral containment or mortality. These results suggest that, in contrast to HIV-1-infected adults, in whom strong cytotoxic T lymphocyte responses in primary infection are associated with reductions in viremia, HIV-1-infected neonates generate HIV-1-specific CD8<jats:sup>+</jats:sup>-T-cell responses early in life that are not clearly associated with improved clinical outcomes.</jats:p>