Our findings indicate that ApoE4 is less effective than ApoE2 or ApoE3 in restricting Tat-induced HIV-1 LTR transactivation in glioblastoma, ApoE mimetic peptide could be used as a therapeutic strategy against HIV-1 infection and associated neurocognitive disorders, and ApoE4 structure correctors could be used as a therapeutic strategy in HIV-1 positive people having the APOE4 allele. This evidence concerns the gene APOE and glioblastoma.