Altogether, whereas the associations with viral load were more complex and not significant for NLRP3, our data support that HIV infection induces IFI16 in human monocytes, and both IFI16 and NLRP3 expression is higher in PWH with more pronounced immunodeficiency (i.e., with lower CD4 T cell counts). Here, NLRP3 is linked to immunodeficiency disease.