Maternal plasma and breastmilk viral loads are associated with HIV‐1‐specific cellular immune responses among HIV‐1‐exposed, uninfected infants in Kenya

Summary Infants exposed to maternal HIV‐1 provide an opportunity to assess correlates of HIV‐1‐specific interferon (IFN)‐γ responses and may be informative in the development of HIV‐1 vaccines. HIV‐1‐infected women with CD4 counts 200–500 cells/mm 3 were randomized to short‐course zidovudine/nevirapine (ZDV/NVP) or highly active anti‐retroviral therapy (HAART) between 2003 and 2005. Maternal plasma and breastmilk HIV‐1 RNA and DNA were quantified during the first 6–12 months postpartum. HIV‐1 gag peptide‐stimulated enzyme‐linked immunospot (ELISPOT) assays were conducted in HIV‐1‐exposed, uninfected infants (EU), and correlates were determined using regression and generalized estimating equations. Among 47 EU infants, 21 (45%) had ≥1 positive ELISPOT result during follow‐up. Infants had a median response magnitude of 177 HIV‐1‐specific spot‐forming units (SFU)/106 peripheral blood mononuclear cells (PBMC) [interquartile range (IQR) = 117–287] directed against 2 (IQR = 1–3) gag peptide pools. The prevalence and magnitude of responses did not differ by maternal anti‐retroviral (ARV) randomization arm. Maternal plasma HIV‐1 RNA levels during pregnancy (P = 0·009) and breastmilk HIV‐1 DNA levels at 1 month ( P  = 0·02) were associated with a higher magnitude of infant HIV‐1‐specific ELISPOT responses at 1 month postpartum. During follow‐up, concurrent breastmilk HIV‐1 RNA and DNA (cell‐free virus and cell‐associated virus, respectively) each were associated positively with magnitude of infant HIV‐1‐specific responses ( P  = 0·01). Our data demonstrate the importance of antigenic exposure on the induction of infant HIV‐1‐specific cellular immune responses in the absence of infection.