Treatment of HIV-infected macrophages with PI3K/Akt inhibitors reduces HIV-1 production and induces cell death. Primary human macrophages were infected with HIV-1 YU-2 and either left untreated (media only) or were treated with one of four different PI3K/Akt kinase inhibitors in the presence or absence of stress (SNP, 1 mM): (A) the PI3K inhibitor wortmannin (100 nM), (B) Akt inhibitor IV (200 nM), (C) Akt inhibitor VIII (105 nM) or (D) Miltefosine 5 μM. Viral supernatants were collected every 3 days for 12 days and supernatants were analyzed using the HIV-1 p24 EIA. Asterisks denote undetectable p24 levels. (E) On day 12, YU2-infected macrophages were analyzed for cell viability using the live/dead assay. Viable cells are green; dead cells are red. Results are representative of 5 independent, triplicate experiments using cells obtained from multiple blood donors. BF: Bright field. Merge: overlay of red and green fluorescence. The average ± SD percentage of dead cells is also shown.