Pro-apoptotic signaling events that can be activated by opiate drugs and HIV, and potential sites of convergence underlying synergistic neurotoxicity. Potential sites where opioids impact Tat/gp120-mediated neurotoxicity include PI3-kinase, PTEN, Akt, Ca2+, calcineurin, BAD, GSK3β, caspase-3 and endonuclease-G (endo-G) (arrows indicate activation; lines ending in “T” indicate inhibition; broken arrows indicate multi-step and/or incompletely understood pathways; pathways & abbreviations are noted in the text).