Drug-antibody conjugates with anti-HIV activity

Human immunodeficiency virus (HIV)-specific peptide antibody-brefeldin A co njugates and antibody-glaucarubolone conjugates directed to cell surface vi ral glycoprotein epitopes were prepared and tested for antiviral activity. A selective response was observed both on survival of cell lines permanentl y infected with lentiviruses and on HIV infectivity. With human peripheral blood mononuclear cells (PBMCs), the conjugate also was effective in reduci ng virus titers. The effectiveness of an HIV-specific peptide antibody-bref eldin A conjugate was enhanced by combination with 3'-azido-3'-deoxythymidi ne (AZT) and was effective against AZT-resistant isolates in combination wi th AZT. The conjugates reduced virus production in MOLT-4 cells and in HIV- 1-infected PBMCs without affecting the viability of uninfected cells. BIOCH EM PHARMACOL 58;11:1781-1790, 1999. (C) 1999 Elsevier Science Inc.