There are two proposed mechanisms as to how HIV-1 may cause GBM: one is via immunosuppression, which has been directly linked to GBM by a mechanism of decreasing anti-tumor activity and thus promoting the development of malignancies; and the other mechanism is via HIV regulator genes such as negative factor (Nef) and trans activator of transcription (Tat). This evidence concerns the gene TAT and glioblastoma.