Tat also inhibits the pro-apoptotic proteins p53 and the Bcl2-associated antagonist of cell death (BAD).40 Nef causes p21-activated kinase activation, leading to phosphorylation of BAD, thus inhibiting its pro-apoptotic activity (binding to and inhibition of Bcl2),44 and also inhibits caspase-8 and caspase-10.40 Conversely, in the CNS, it appears that Tat and Nef may induce autophagy and apoptosis in HAND pathogenesis.45,46 Expression and activation of anti-apoptotic proteins are therefore increased in latently infected cells, making this an attractive therapeutic target. Here, TAT is linked to HIV-associated neurocognitive disorder.