This study was aimed at identifying generic drugs with activity against HIV. It has two components; computational and in-vitro studies. The computational study entails sequential screening of all FDA approved drugs (1491) against three protein targets; through structural- and ligand- based pharmacophore screening followed by molecular docking of the selected drugs against the viral targets. Two (2) drugs with the best binding affinities against the viral targets were chosen for an in-vitro confirmation of activity. The non-toxic concentrations used for the study were established from MTT cytotoxicity study using Cmax of the drugs as a guide. Iodixanol and sirolismus had the best binding affinities against the three viral targets. Again,iodixanol and sirolismus produced a concentration dependent viral killing in the antiviral studies. Iodixanol produces significant anti-HIV virucidal effect (%VI =43.3) at 1000 µg/ml not different from the effect by Zidovudine (%VI = 45.3).