Synergistic effect resulting from combinations of a bifunctional HIV-1 antagonist with antiretroviral drugs.

Development of new anti-HIV therapeutics remains necessary for patients with HIV/AIDS who fail to respond to the current antiretroviral drugs. In this study, we investigated the potential cooperative effects of 2DLT, a bifunctional HIV-1 antagonist with viral inactivation and fusion inhibition activities, combined with different antiretroviral drugs, including HIV entry inhibitors, nucleoside and nonnucleoside reverse-transcriptase inhibitors (NRTIs and NNRTIs), and protease inhibitors. We found that combining 2DLT with these antiretroviral drugs resulted in synergism or strong synergism against infection by both X4 and R5 HIV-1 strains. Although 2DLT alone is highly effective against both NRTI- and NNRTI-resistant HIV-1 strains, combining 2DLT with zidovudine, stavudine, or nevirapine resulted in synergistic or strong synergistic antiviral effect against single or multiple RTI-resistant HIV-1 strains, suggesting that 2DLT can be further developed as a novel anti-HIV-1 drug for addition to the highly active antiretroviral therapy regimen for salvage therapy of patients with HIV/AIDS who are refractory to current antiretroviral drugs.