Merck & Co.’s anti-HIV drug, Isentress, is effective against a recently discovered retrovirus called XMRV (xenotropic murine leukemia-related retrovirus) that has been linked with prostate cancer and chronic fatigue symdrome (CFS), report researchers from the University of Utah and Emory University/Veterans Affairs Medical Center. They suggest that if XMRV can be shown to have a causative role in these two diseases, they may be treatable with an existing medication.
The findings are published in PLoS ONE in a paper titled “Raltegravir is a potent inhibitor of XMRV, a virus implicated in prostate cancer and chronic fatigue syndrome.”
The group, led by Ila R. Singh, M.D., Ph.D., associate professor of pathology at the University of Utah School of Medicine, tested 45 antivirals including 28 marketed drugs in cultured human breast cancer and prostate cancer cells. They found that the integrase inhibitor, raltegravir (the API in Isentress), was the most potent XMRV inhibitor, although another integrase inhibitor L-000870812 and the nucleoside reverse transcriptase inhibitors zidovudine and tenofovir disoproxi fumarate also blocked XMRV replication.
When combined, the compounds also displayed synergistic effects and required even lower doses to be effective. This further throws up the possibility that mix-and-match approaches to treating XMRV infection could be a useful tool against the emergence of resistant viruses, the authors point out.
The researchers do admit that there is still much to find out about XMRV’s putative role in prostate cancer and CFS. “Not all studies that have looked for XMRV have been able to detect it in prostate cancers or in samples from CFS,” they poins out. “Even if XMRV is established to be the cause of prostate cancer or CFS, we will need to see the results of clinical trials before these drugs can be used in a clinical setting.”
Nevertheless, they conclude, “when an assay to measure XMRV viral loads becomes available, virus levels in the blood might become an objective surrogate marker for an effective response to antiviral drugs in addition to clinical outcomes.
“While it is not yet clear if any illnesses are directly caused by XMRV, our data indicates that XMRV infections might be prevented or treated with specific antiviral agents. In the presence of any evidence of causality of human disease, our findings should provide the basis for designing clinical trials to treat them.”
While Merck’s Isentress was shown to be the most effective drug out of those tested in terms of blocking XMRV, the reported study was not supported by the company or by any other antiviral drug manufacturer, the researchers state.