Background:  Mother-to-child perinatal HIV transmission leads to rapidly progressing infection and immune deficiency. To date, very little is known on the effects of viral replication on dendritic cell (DC), natural killer (NK) cell, and T cell subsets in infants.

Methods:  We studied a total of 69 infants (<180 days old; HIV-infected:  n = 50; HIV-exposed, uninfected n = 19). Of 50 HIV⁺ subjects, 23 had plasma HIV-1 RNA (viral load) >5000 copies/mL (high viral load group) and 27 had vrial load <5000 (low viral load group). All HIV⁺ infants participated in the CIPRA-SA Children with HIV Early ART (CHER) trial in South Africa, but analyses were not undertaken by randomized arm in this cross-sectional study. Clinical (CD4%, viral load) and immune (T, NK, and DC) variables were assessed on fresh whole blood samples. Multiple flow-based analysis allowed for immune subset characterization. Between-group comparisons were done using the Wilcoxon/Kruskal-Wallis test. Correlations between variables were assessed using Spearman test.

Results:  As expected, comparison of HIV groups showed lower CD4% and CD28% and higher CD8% and T cell activation (CD38% T cells and CD38 surface expression, primarily on CD8⁺ T cells) in the high viral load group, while controls had lower CD8% and activation, but higher CD4% and CD28% T cells than HIV⁺ groups. Interestingly, distribution of naïve/memory cell subsets indicated that children in the high vl group had a higher frequency of naïve and lower frequency of central memory/effector intermediate CD4⁺ T cells, while as expected, the opposite was observed for the CD8⁺ T cells. In addition, CD3⁺/CD4^–/CD103⁺/CD28⁺ and CD3⁺/CD4^–/CD184⁺ % of CD4^- T cells  were higher in both HIV groups compared to uninfected controls, while no difference was observed for the same subsets for CD4⁺ T cells or for CD195⁺ T cells. Regarding innate cells, CD161⁺/CD56^–/CD16⁺, CD161⁺/CD56⁺/CD16^–, CD56⁺CD16⁺/CD195⁺ % of NK and both plasmacytoid and myeloid DC subsets were higher in HIV⁺ infants compared to the control group. These results were also confirmed by correlation analysis.

Conclusions:  We report for the first time in HIV-infected infants of <6 month old and in contrast to acute infection in adults, an increase in circulating naïve CD4⁺ T cell and retention of innate effectors in the presence of high viral replication and T cell activation. Data indicates that newborns respond to infection with a compensatory response which is more likely to be maintained under viral suppression.