HIV drug may help in PML(31/01/14)

A relatively simple way to make progressive multifocal leukoencephalopathy (PML) more survivable appears to have worked in a multiple sclerosis patient taking natalizumab (Tysabri).

Before telling you what that remedy is, first let's go over what happens in PML. Those already familiar with it and a related condition called IRIS can skip over this part.

PML is a severe brain inflammation arising from reactivation of latent infection with the so-called JC virus, which is common in the general population. This reactivation usually results from some type of immunosuppression -- PML has been seen in conjunction with cancer chemotherapy, HIV infection, and with certain drugs targeting particular immune-system components.

Although natalizumab has attracted the most attention recently for PML risk, the condition has been linked to other drugs, including rituximab (Rituxan), fingolimod (Gilenya), and others.

With natalizumab-related PML, the death rate has been about 20%, and many patients who have survived show permanent neurocognitive deficits. Consequently, clinicians want to treat it aggressively. The normal treatment is plasmapheresis, in order to remove natalizumab (which has a long half-life) from circulation as quickly as possible, restoring immune function and suppression of the JC virus.

Unfortunately, the sudden removal of natalizumab often triggers a condition called immune reconstitution inflammatory syndrome (IRIS), which is practically as dangerous as PML. Many of the deaths and persistent deficits attributed to PML actually are a consequence of IRIS.

Amit Bar-Or, MD, of McGill University in Montreal, and colleagues reported in the New England Journal of Medicine this week that oral maraviroc (Selzentry), a CCR5 chemokine receptor antagonist for treating certain forms of HIV infection, helped a 49-year-old woman with MS avoid IRIS following plasmapheresis. The woman had undergone plasmapheresis because she had developed PML while taking natalizumab.

The treatment had two inspirations. One was bench research that implicated the CCR5 receptor as important to immune cell populations that contribute to IRIS. The other was a 2009 case report from France in which an HIV patient who developed PML and IRIS (which can paradoxically develop in HIV patients in the absence of plasmapheresis) responded well to maraviroc, which had been administered because it was supposed to have vague "immunomodulating properties."

Bar-Or and colleagues started the woman on maraviroc shortly after plasmapheresis. For 2 months, she showed no "clinical or imaging evidence of overt IRIS," they wrote.

She then stopped taking the maraviroc for 5 days, at which point she developed clear neurocognitive symptoms and showed IRIS-like features on brain MRI scans. Her doctors restarted the maraviroc and the symptoms and brain lesions abated, but she was left with some mild but permanent cognitive deficits.

It's too early to say whether maraviroc will become a standard part of PML treatment. On the other hand, for clinicians with PML patients on their hands, it seems likely that many if not most will give maraviroc a try -- given the risks of not trying.

Several authors of the report had relationships with pharmaceutical companies that sell MS drugs, including natalizumab's manufacturer, Biogen Idec. None reported a relationship with maraviroc's manufacturer, ViiV Healthcare.

Source: MedPage Today © 2014 MedPage Today, LLC (31/01/14)