A new acyclic heterodinucleotide active against human immunodeficiency virus and herpes simplex virus

The most common therapies against human herpes virus (HSV-1) and human immu nodeficiency virus (HIV-I) infectivity are based on the administration of n ucleoside analogues. Acyclovir (ACV) is the drug of choice against HSV-I in fection, while the acyclic nucleoside phosphonate analogue PMPA has shown m arked anti-HIV activity in a phase I and II clinical studies. As monocyte-d erived macrophages are assumed to be important as reservoirs of both HSV-1 and HIV-1 infection, new approaches able to inhibit replication of both vir uses in macrophages should be welcome. ACVpPMPA, a now heterodinucleotide c onsisting of both an antiherpetic and an antiretroviral drug bound by a pho sphate bridge! was synthesized and encapsulated into autologous erythrocyte s modified to increase their phagocytosis by human macrophages. ACVpPMPA-lo aded erythrocytes provided an effective in vitro protection against both HS V-I and HIV-1 replication in human macrophages. (C) 2000 Elsevier Science B .V. All rights reserved.