The persistence of latent reservoirs of human immunodeficiency virus type 1 (HIV-1) represents a major barrier to virus eradication in patients on
combination antiretroviral therapy. It has been suggested that treating infected individuals simultaneously with
highly active antiretroviral therapy (
HAART) and agents that activate cells to express HIV-1 might eliminate these latent reservoirs. The
phorbol ester prostratin, used in Western Samoa as an ethno-botanical treatment for viral
hepatitis, was isolated at the National Cancer Institute in 1992.
Prostratin represents a distinct subclass of
protein kinase C activators, since unlike other
phorbol esters it does not induce
tumor formation.
Prostratin upregulates expression of viral products from latently infected cells such as U1, ACH-2 and peripheral blood mononuclear cells from patients on
HAART with undetectable plasma
viremia. It also inhibits
HIV infection and viral spread at the entry/fusion step of viral life cycle. The lack of
tumor promotion of
prostratin coupled with its ability to upregulate latent HIV-1 provirus expression and inhibition of
viral infection are important features that could be exploited as effective
therapy to eliminate latent reservoirs.