Survival in patients with PML longer with protease inhibitor and cidofovir treatment

A case series published in the 21^st March edition of AIDS has suggested that HIV-positive patients with progressive multifocal leukoencephalopathy (PML) survive longer if they are treated with antiretroviral therapy including a protease inhibitor as well as the anti-viral drug cidofovir (Vistide).

PML is brain disease that is caused by the JC virus. Although it is very rare in the general population, it is more common in patients with HIV, affecting up to 4% of patients with AIDS.

Although modern anti-HIV drug combinations have improved survival, the outlook for patients with a PML diagnosis is very poor, since the best treatments for the disease have not been established. Recent studies have shown median survival times of between 131 and 646 days, with up to 46% of patients dying within twelve weeks of diagnosis.

Now, a team of doctors from St Mary’s Hospital in London have reported longer survival times in four HIV-positive patients with PML who were treated with protease inhibitors and intravenous cidofovir at their clinic between 1998 and 2005.

The four patients presented with symptoms of PML, including weakness, headaches, speech impairment, altered vision and weight loss. The doctors confirmed PML by detection of JC virus in the brain fluid, by brain scans or by analysis of small samples of brain tissue under the microscope.

After PML diagnosis, three of the patients started an anti-HIV drug combination including a protease inhibitor. The fourth patient added the protease inhibitor ritonavir-boosted lopinavir (Kaletra) to her existing treatment regimen.

All of the patients also received intravenous infusions of cidofovir for at least six weeks.

All the patients all showed an improvement in their PML symptoms, with survival reaching between 691 and 2839 days. They all showed an improvement in CD4 cell counts, but showed no side-effects of cidofovir treatment.

“All patients remain alive and have made significant and in three cases dramatic recoveries after therapy,” write the doctors. “We report the longest median survival ... to date yet published of a patient with confirmed PML.”

The doctors point out that all four patients had a deterioration of their symptoms after they started antiretroviral therapy, but that their conditions improved after they started cidofovir treatment. “Although this may be the result of the inhibition of JC virus replication by cidofovir another possibility is increased inflammation caused by HAART-induced immune reconstitution that resolved spontaneously,” they explain.

Although the description of individual medical case histories can provide interesting information on diseases and treatments, their findings should be interpreted with caution, since there is no group of ‘control’ patients with which to compare outcomes. Case series may also fail to pick up other factors that are linked to the patients’ outcomes.

“The role of cidofovir should be confirmed by a randomised clinical trial,” the doctors conclude, “but this may not be possible given the small number of new PML diagnoses.”