Methods for selecting transgenic cells comprising two or more drug resistance genes with a combination of cytotoxic drugs (e.g., trimetrexate (TMTX) and hydroxyurea (HU)). Such selection can be completed in vitro or in vivo. Transgenic cells and vectors comprising combinations of resistance genes are also provided. Transgenic cells of the embodiments can be used as cell based therapeutics, such as for treatment of HIV infection.