Inhibition of Murine AIDS by Combination of AZT and DDCTP-Loaded Erythrocytes

Abstract

The human acquired immunodeficiency syndrome (AIDS) is a complex disease induced by the human immunodeficiency virus (1, 2). The development of effective therapies for AIDS has been limited by the lack of animal models that exactly mimic events in human disease. Murine AIDS (MAIDS) is a disease that shares many similarities with human AIDS such as splenomegaly, hypergammaglobulinemia, lymphoadenopathy, T- and B-lymphocyte dysfunctions and profound immunodeficiency (3–5). Since many features of this syndrome are common to those defined in human AIDS, MAIDS serve as a useful experimental model for understanding the pathogenesis of AIDS as well as searching for anti-HIV drugs. In our laboratory this animal model has been used to evaluate the efficacy and toxicity of drugs belonging to the nucleoside analogue family (6, 7), known to be potent in vitro and in vivo inhibitors of HIV-1 replication. Unfortunately, the efficacy of drugs so far used in monotherapy is of limited duration while a number of preliminary studies have already shown that combination therapy is more effective than monotherapy (8, 9). Combination therapy may provide additive or synergistic effect of combined drugs, decreased toxicity and delay of viral resistance. Furthermore, treatment can include drugs acting at different levels of HIV replication or protecting different cell types (i.e. lymphocytes and macrophages). Monocyte/macrophages are important target cells for the human immunodeficiency virus type 1 (HIV-1) (10, 11). They may be chronic recervoirs of HIV-1 and probably play an important role in the pathogenesis of AIDS-related complications such as dementia.