The findings indicate that exposure to METH combined with HIV infection exerts a long-term impact on NPC transcriptomics that is preserved ex vivo and results in enhanced NPC proliferation via the CXCL12/CXCR4/Akt-1-mediated phosphorylation of FOXO3 that regulates FOXO3 target genes. Here, CXCR4 is linked to HIV infectious disease.