Title

Early initiation of anti-retroviral therapy restores some but not all perturbations of natural killer cell functions and phenotypes in early HIV-1 infected men who have sex with men

Presenter

Matrona Akiso

Authors

M. Akiso¹, R. Langát², D. Muema², K. Naidoo³, G. Oino², T. Kotikot², G. Mutua², C. Tsabalala³, D. Ochiel⁴, K. Chinyenze⁴, O. Anzala^2,1, M. Mureithi^1,2

Institutions

¹University of Nairobi, Department of Medical Microbiology, Nairobi, Kenya, ²KAVI Institute of Clinical Research, Department of Medical Microbiology, Nairobi, Kenya, ³University of KwaZulu-Natal, HIV Pathogenesis Programme, Durban, South Africa, ⁴International AIDS Vaccine Initiative, Nairobi, Kenya

BACKGROUND: NK cells play a crucial role in regulating HIV-1 infection and replication, and this regulation of HIV-1 infection and replication may determine the disease outcome. Antiretroviral therapy (ART) effectively restores CD4+ T cell counts and suppresses HIV-1 viral loads to undetectable levels in circulation. However, it is unclear whether or not the perturbations on NK cells are fully recovered. We hypothesized that early initiation of ART restores NK cell perturbations due to HIV-1 infection. We, therefore, sought to understand the phenotypic and functional changes that may occur to NK cells in early HIV-1 infection and whether early initiation of ART restores these possible changes.
METHODS: We longitudinally evaluated NK cell functional and phenotypic changes in early HIV-1 infected Men who have Sex with Men (MSM) in Nairobi, Kenya, and who were recently initiated on ART. Blood samples were obtained fortnightly for three visits post seroconversion. Baseline blood samples collected in the SiVET study before seroconversion were also analyzed. Frozen PBMCs were thawed and stimulated overnight with K562 cell line, IL-2 and IL-15 and stained with antibodies to evaluate NK cell phenotype, activation, and functionality.
RESULTS: Compared to the pre-seroconversion time point, there were no changes in the total NK cell frequencies across the time points. We observed significant reductions in NK cell production of IFN-?, expression of CD69, and NK cell inhibitory receptor siglec7. However, there were significant increases in NK cell degranulation and expression of cell exhaustion marker PD-1. Most of these changes were restored to near the pre-seroconversion level around 30 days post-ART initiation. The reduction in expression of the siglec7 receptor was, however, not restored.
CONCLUSIONS: The impairment of NK functionalities in early HIV-1 infection may enhance disease progression. This could be one way in which HIV-1 escapes the immune system. However, these impairments seem to be restored a few weeks after ART supporting the test and treat strategy. Evaluating the mechanisms by which HIV-1 impairs NK cell effector functions would inform designing an effective HIV-1 vaccine boosting innate immunity.

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