Homopurine:homopyrimidine stretches of dsDNA can form triple helices with homopyrimidine oligonucleotides. Triple helical structures prevent transcription and translation across their sequences. We have designed several homopyrimidine oligonucleotides which target specific HIV-1 genes (gag, pol, tat, rev, nef). Studies will assess the affects of these oligos (added to media as is or in liposomes) on HIV-1 infection in H9 and U937 cells. Additional constructs attaching intercalating agents to HIV- targeted oligos are being designed.