April 12, 2010

HIV Drugs Also Target Prostate Cancer and Chronic Fatigue Virus

Four antiretrovirals (ARVs), notably Merck’s integrase inhibitor Isentress (raltegravir), can inhibit a virus linked to prostate cancer and chronic fatigue syndrome, according to a press release from Emory University in Atlanta highlighting a paper published online earlier this month by the journal PLoS ONE. 

Discovered in 2006, xenotropic murine leukemia virus (XMRV) has been detected in some prostate cancer patients’ tumor biopsies. However, its precise role in driving prostate cancer is unclear. In addition, a research team at the Whittemore Peterson Institute in Nevada has suggested that XMRV is the causative agent of chronic fatigue syndrome in a majority of patients. However, other laboratories have yet to confirm these results.

“Not all studies that have looked for XMRV have been able to detect [the virus] in prostate cancers or in samples from chronic fatigue syndrome,” says Ila Singh, MD, PhD, associate professor of pathology at the University of Utah School of Medicine and a study collaborator. 

Singh led another recently published study demonstrating the presence of XMRV in 27 percent of prostate cancers examined, with the virus more likely to be found in the most-aggressive tumors. XMRV may promote cancer by integrating into the host cell DNA and warping the cell’s ability to regulate its own genes.

Although both XMRV and HIV are retroviruses, there is little similarity between HIV and XMRV at the protein level. Yet there are only a few retroviruses known to infect humans—human T-lymphotropic viruses 1 and 2, HIV and now XMRV—with similar traits and treatment approaches. 

Singh and Raymond Schinazi, PhD, DSc, professor of pediatrics and chemistry at Emory’s Center for AIDS Research and the Atlanta VAMC, and their colleagues teamed up to test 45 approved and experimental ARVs and other antiviral compounds against XMRV in cell culture.

The most potent drug against XMRV was Isentress, originally approved in 2007 for treatment-experienced patients. 

Besides raltegravir, three other compounds—another integrase inhibitor in addition to zidovudine (found in Retrovir, Combivir and Trizivir) and tenofovir (found in Viread, Truvada and Atripla), two reverse transcriptase inhibitors—also inhibit XMRV replication. These ARVs, the Emory and University of Utah researchers suggest, could be used together in combination therapy, much like they’re used to treat HIV. 

None of the protease inhibitors stopped XMRV in test tube studies. 

“Our study showed that these drugs inhibited XMRV at lower concentrations when two of them were used together, suggesting that highly potent ‘cocktail’ therapies might inhibit the virus from replicating and spreading,” Schinazi said. “This combination of therapies might also have the added benefit of delaying or even preventing the virus from mutating into forms that are drug-resistant.”

 “We will need to see the results of clinical trials before these [HIV] drugs can be used in a clinical setting,” Singh said.

Search: xenotropic murine leukemia virus, XMRV, antiretrovirals, prostate cancer, chronic fatigue syndrome, CFS, raltegravir, Isentress, zidovudine, tenofovir, Singh, Schinazi, Emory, Utah

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Previous Comments:

Dave, New York City, 2010-04-15 16:52:49
Will Isentress get another 20 patent starting in 2010? I'm sure.

Oscar Torres, Nolanville, TX, 2010-04-14 21:07:16
This is a very interesting article, because I can say that since I have started my medications in 2005. I've been more tired than when I did not take these meds at all. Sometimes it gets very irritating knowing that you get tired more easily and there are many things you did before and can't do because of the fatigue that these medications cause. I can't complain they have done me good in a sense of reducing my viral load and increasing my CD4 count from what it was back in March 2005.

Salmonid, , 2010-04-12 22:54:51
Just a minor correction on retroviruses that infect humans. There are HTLVs 1, 2, 3, and 4, HIV-1 and 2, and HFV. Lab workers have been infected with SIV and other animal retroviruses. There have also been several reports of mouse retroviruses in humans or human cells before XMRV. Then there are the endogenous retroviruses, mostly inactive now, but making up about 7 to 8% of our genome!