1031 – NK Cell KIR Education Is Associated With Low HIV DNA Load in Early ART-Treated Children

Background

Early ART initiation, low immune activation, and effective anti-HIV NK cell responses have been linked with HIV remission in adults. It has been proposed that these features in combination with early life immunity may favour remission in children living with HIV (LWH). In a cohort of very early ART-treated children in KwaZulu-Natal, South Africa, we here examined the immunogenetic signatures and functional NK cell profile associated with low HIV DNA load and increased HIV cure/remission.

Methods

We evaluated a cohort of >300 early-ART-treated children LWH from KwaZulu-Natal, South Africa followed from birth. The cohort included 5 ‘atypical’ children who maintained ART-free aviraemia following unscheduled ART discontinuation. Total HIV DNA was quantified longitudinally as a proxy for reservoir size. NK cell function was assessed via immunophenotypic analysis and stimulation with IL-12/IL-18, K562 cells and Rituximab-coated Raji cells.

Results

Low HLA-A expression, favouring KIR-educated NK cells, was associated with low total HIV DNA load at birth and at 9m age (p=0.01 and p=0.01). Also, consistent with adult post-treatment controller (PTC) cohorts, children with ‘protective’ HLA-B alleles (HLA-B*57/58:01/81:01) had 0.5 log₁₀ higher total HIV DNA loads at birth and 9m (p=0.02 and p=0.04) than those without. High NKG2D expression on CD56^dim NK cells, potentially reflecting heightened inflammation and increased soluble NKG2D ligands such as sMIC-A and sMIC-B, correlated with low HIV DNA (r=-0.51, p=0.005) at 9m age. Following IL-12/IL-18 stimulation, high IFNg production by NKG2A+CD56^dim NK cells was associated with low HIV DNA loads (r=-0.6, p=0.01) at 9m, and spontaneous CD107a production by iKIR+NKG2A-CD56^dim NK cells negatively correlated with HIV DNA load at 9m and 30m (p=0.01 and p=0.01). Unexpectedly, NK cells in the 5 ‘atypical’ children expressed higher iKIR:NKG2A ratio (p=0.05), suggesting a more differentiated NK cell compartment in ‘atypical’ versus ‘typical’ children.

Conclusions

These data suggest that an HLA-I signature favouring KIR-educated NK cells is associated with low total HIV DNA load in early ART-treated children at birth, implying in utero anti-HIV NK cell activity. This HLA-I signature is consistent with findings from ART-naïve adults, ART-naïve children and adult PTCs. These data also indicate a diverse pattern of CD56^dim NK cell functionality mediating reduced HIV DNA load and increased HIV cure/remission potential in children.

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