We have observed significantly increased HIV infection in HIV infected macrophages in the presence of cocaine that could be due to the downregulation of BST2 restriction factor in these cells. In human inflammasome PCR array, among different involved in inflammasome formation, in HIV infected macrophages in the presence of cocaine, we have observed significant upregulation of NLRP3, AIM2 genes and downstream genes IL-1β and PTGS2. Whereas negative regulatory gene MEFV was upregulated, CD40LG and PYDC1 were significantly downregulated. Among various NOD like receptors, NOD2 was significantly upregulated in both HIV alone and HIV plus cocaine treated cells. In the downstream genes, chemokine (C-C motif) ligand 2 (CCL2), CCL7 and IL-6 were significantly up regulated in HIV plus cocaine treated macrophages. We have also observed significant ROS production (in HIV and/or cocaine treated cells) which is one of the indirect-activators of inflammasomes formation. Further, we have observed early apoptosis in HIV alone and HIV plus cocaine treated macrophages which may be resultant of inflammasome formation and cspase-1 activation. These results indicate that in case of HIV infected macrophages exposed to cocaine, increased ROS production and IL-1β transcription serve as an activators for the formation of NLRP3 and AIM2 mediated inflammasomes that leads to caspase 1 mediated apoptosis.