Many upregulated genes in the H+C+ signature (non-LLT users) have known roles in HIV infection, including several innate immune response genes previously shown to be stimulated by HIV in vitro (IFIT1/2/3, DDX58, MX1) [25], CCL3 and CCL4L2, which encode macrophage inflammatory protein-1 alpha and beta [26], complement factor B (CFB) of the alternative complement pathway [27, 28], interleukins/ interleukin receptors (IL7, IL18, IL15RA) and the interferon-stimulated genes e.g., ISG15, ISG20, USP18 [29]. Here, ISG15 is linked to HIV infectious disease.