Compounds are disclosed for treating viral infections due to herpes, influenza, hepatitis B, Epstein-Barr, and varicella zoster viruses, as well as cytomegalovirus and human immunodeficiency virus (HIV) by means of lipid derivatives of antiviral agents. The compounds consist of lipid derivatives of phosphonoacids having antiviral activity which are linked, commonly through the phosphate group of the phosphonoacid, to one of a selected group of lipids.
The lipophilic nature of these compounds provides advantages over the use of the phosphonoacids alone. It also makes it possible to incorporate them into the lamellar structure of liposomes when combined with similar molecules. In the form of liposomes, these antiviral molecules are preferentially taken up by macrophages and monocytes, cells which have been found to harbor the target human immunodeficiency virus (HIV). Additional site specificity may be incorporated into the liposomes with the addition of ligands, such as monoclonal antibodies or other peptides or proteins which bind to viral proteins.
Effective phosphonoacids are phosphonoformic acid or phosphonoacetic acid; lipid groups may be glycolipids, sphingolipids, phospholipids, glycerolipids, or fatty acids. The compounds persist, after intracellular hydrolysis, as the antiviral phosphonoacids. The compounds are effective in improving the efficacy of antiviral phosphonoacids by prolonging the antiviral activity after the administration of the drug has ended, and in preventing retroviral replication in HIV infections which have become resistant to therapy with conventional forms of the antiretroviral agents.