Innate immune imprints shape HIV-1 reservoir cell persistence during long-term antiretroviral therapy.

HLA-C2 allotypes and KIR2DL1+ NK cells significantly reduce HIV-1 reservoir cell persistence during long-term antiretroviral therapy, with a notable impact on intact proviruses.

• Why it matters: Understanding immune factors that target HIV-1 reservoir cells is crucial for developing effective cure strategies, especially since these reservoirs persist despite therapy and are poorly targeted by current treatments.
• What they did: Analyzing over 6,000 proviral DNA samples from 104 individuals on long-term antiretroviral therapy, the study examined host genetic markers and NK cell populations, focusing on HLA-C2, KIR2DL1, and viral variants affecting immune recognition.
• The result: Findings reveal that certain host and viral genetic variations enhance NK cell-mediated clearance of reservoir cells, suggesting innate immunity can be harnessed to reduce HIV persistence and inform cure approaches.