Therapy of AIDS-associated Kaposi's sarcoma: targeting pathogenetic mechanisms

The growing understanding of the interplay between human herpesvirus-8 (HHV-8), HIV type 1 (HIV-1), inflammatory cytokines, and angiogenic factors in the pathogenesis of AIDS-associated Kaposi's sarcoma (KS) provides a coherent (but as yet incomplete) framework for the development of therapeutic strategies that target the mechanisms involved in KS development and progression. There is strong evidence that control of HIV-1 infection can lead to KS regression in some patients, but the mechanism is not defined. Administration of inhibitors of HHV-8 lytic replication is associated with a decrease in subsequent KS incidence, but rarely leads to regression of established KS, which contains primarily latent virus. Thus far, a limited number of clinical trials have been performed with agents that may inhibit cytokines and angiogenic factors associated with KS, and although therapeutic activity has been observed with a number of agents with different targets, many therapeutic approaches remain to be investigated. Given the redundancy of growth factors believed to be involved in K development, it is likely that combinations of agents that target several pathogenetic mechanisms will be more effective than are single drugs in suppressing KS growth.