Actinomycin D Stimulates HIV Replication
January 24, 2003
US researchers warn that the anticancer drug actinomycin D (ActD) should not be used to treat HIV patients. "ActD has been reported to be a potential inhibitor of human immunodeficiency virus type 1 (HIV-1) replication due to its ability to inhibit reverse transcription," according to Tomozumi Imamichi and colleagues at Science Applications International Corporation-Frederick Inc. and the National Cancer Institute in Frederick, and the National Institutes of Health in Bethesda, Md.Adapted from:
However, the authors reported, they found that ActD treatment actually enhanced HIV replication in some leukemic cells. The researchers added low doses of ActD to HIV-infected MT-2 human T-lymphoma cell cultures. ActD treatment augmented HIV replication in those cells by up to tenfold, they found. Study data also showed that MT-2 cells treated with ActD demonstrated strong resistance to thymidine analogs such as zidovudine and stavudine although their susceptibility to other classes of antiretroviral agents was unaffected. According to the data, this result was apparently linked to ActD-induced downregulation of thymidine kinase (TK)-1.
ActD treatment had no effect on HIV replication in other leukemic cell lines or in healthy peripheral blood mononuclear cells, Imamichi and colleagues wrote. The full report, "Actinomycin D Induces High-Level Resistance to Thymidine Analogs in Replication of Human Immunodeficiency Virus Type 1 by Interfering with Host Cell Thymidine Kinase Expression" was published in the Journal of Virology (2003;77(2):1011-1020).
"These results suggest that administration of combination drugs to HIV-1-infected patients may induce resistance to antiretroviral compounds via a modification of cellular factors," Imamichi and colleagues concluded.
01.04.03; Michael Greer