Miltefosine is a phospholipid drug. Miltefosine is usedfor the treatment of visceral and cutaneous leishmaniasis. Several medical agents have some efficacy against visceral or cutaneous leishmaniasis, however a 2005 survey concluded that miltefosine is the only effective oral treatment for both forms of leishmaniasis. Miltefosine targets HIV infected macrophages, which play a role in vivo as long-lived HIV-1 reservoirs. The HIV protein Tat activates pro-survival PI3K/Akt pathway in primary human macrophages. Miltefosine acts by inhibiting the PI3K/Akt pathway, thus removing the infected macrophages from circulation, without affecting healthy cells. It significantly reduces replication of HIV-1 in cocultures of human dendritic cells (DCs) and CD4(+) T cells, which is due to a rapid secretion of soluble factors and is associated with induction of type-I interferon (IFN) in the human cells.
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