Infants with late breast milk acquisition of HIV‐1 generate interferon‐gamma responses more rapidly than infants with early peripartum acquisition

Infants infected with HIV‐1 after the first month of life have a lower viral set‐point and slower disease progression than infants infected before 1 month. We investigated the kinetics of HIV‐1‐specific CD8+ T lymphocyte secretion of interferon (IFN)‐γ in infants infected before 1 month of life compared with those infected between months 1 and 12 (late infection). HIV‐1 infection was assessed at birth and at months 1, 3, 6, 9 and 12 and timing of infection was determined by HIV‐1 gag DNA from dried blood spots and verified by plasma HIV‐1 RNA levels. HIV‐1 peptide‐specific IFN‐γ responses were measured by enzyme‐linked immunospot at months 1, 3, 6, 9 and 12. Timing of development of IFN‐γ responses was compared using the log–rank test and Kaplan–Meier survival curves. Infants infected late developed HIV‐1‐specific CD8+ T cell responses 2·8 months sooner than infants infected peripartum: 2·3 versus 5·1 months after HIV‐1 infection (n = 52, P = 0·04). Late‐infected infants had more focused epitope recognition than early‐infected infants (median 1 versus 2 peptides, P = 0·03); however, there were no differences in the strength of IFN‐γ responses. In infants infected with HIV‐1 after the first month of life, emergence of HIV‐1‐specific CD8+ IFN‐γ responses is coincident with the decline in viral load, nearly identical to what is observed in adults and more rapid than in early‐infected infants.