HIV-1 Elite Controllers are Characterised by Elevated Levels of CD69-Expressing Natural Killer Cells.

Background: Human immunodeficiency virus type 1 (HIV-1) elite controllers (ECs) are a rare subset of people living with HIV-1 (PLWH) who control viral replication in the absence of antiretroviral therapy (ART) and may provide a model for a functional cure. We investigated the role of natural killer (NK) cells in HIV-1 ECs from South Africa.

Methods: Phenotypic (CD69, CD38, CD57, PD-1), functional (CD107a, IFN-γ), and nutrient transporter profiles (glucose transporter 1, CD98) of NK cells from ECs (n=20), viraemic progressors (VPs; n=19), people living with HIV-1 (PLWH) on ART (n=20), and people without HIV-1 (PWOH; n=21) were analysed using flow cytometry. The Kruskal-Wallis test followed by the Mann-Whitney U test were used to determine differences among the study groups. The Spearman's rank correlation coefficient was used to determine significant associations.

Results: Compared to the other study groups, the percentage of CD69-expressing NK cells was higher in ECs, whereas the percentage of CD38-expressing NK cells was higher in VPs. Percentages of CD69+CD38- NK cells were elevated in ECs compared to VPs (p = 0.003), but were not different to PLWH on ART and PWOH. Differentiation, exhaustion, and metabolic profiles were not different in ECs compared with PLWH on ART and PWOH, however, NK cell function was lower than in PWOH.

Conclusion: These findings demonstrate that NK cells from ECs have an activated, mature profile with low levels of immune exhaustion and a reduced metabolic phenotype suggesting functional competence. This insight could inform the development of novel immunotherapeutic strategies for treating HIV-1.