Special Coverage of the 2000 IDSA Conference

Once uniformly fatal, PML now less dangerous

Research says treat early for best results

Progressive multifocal leukoencephalopathy (PML) was a relentless harbinger of imminent death among some AIDS patients in the first 15 years of the HIV epidemic. Following PML diagnosis, AIDS patients could expect to die within a year. But the situation has changed since 1996 and the advent of highly active antiretroviral therapies (HAART), according to research presented at the Infectious Diseases Society of America conference held in September in New Orleans.

Researchers at the University of Rochester (NY) conducted a retrospective chart review of patients with AIDS-associated PML who were hospitalized from January 1980 to March 2000. They found 34 patients with PML, including three for whom PML was the first HIV manifestation. PML is a demyelinating disease of the brain caused by the JC virus, which is a polyomavirus of the papovirus family. Its symptoms include palsies, seizures, dysarthria, cranial nerve deficits, cortical blindness, quadriparesis, profound dementia, aphasia, and ataxia. 

Those diagnosed in the pre-HAART era had a mean survival time of 309 days after onset of symptoms, vs. those on HAART, who had a mean survival time of 557 days.1 "We wanted to see if antiretrovirals caused any change in PML deaths," says Bogdan Neughebauer, MD, PhD, instructor and fellow in medicine, infectious diseases, at the University of Rochester Medical Center. Neughebauer was an investigator on the study. "The most interesting thing was that there was a very clear advantage for patients on HAART," Neughebauer says. "Those compliant with HAART lived much longer than the patients not on HAART."

Of the PML patients receiving HAART, six are still living some five or six years after their diagnosis. This is remarkable when considering the fact that AIDS patients with PML who receive no antiretrovirals typically die within three to six months, Neughebauer says. "So you can understand our excitement," he adds. "There are patients who survived spontaneously, and this shows that HAART is really doing the job — it’s not a coincidence."

When HIV patients were divided according to whether they were on monotherapy, two antiretrovirals, or three or more combination therapies, researchers found that patients on combination therapies lived longer than those on one or two antiretrovirals, Neughebauer says. "And that group lived longer than those who didn’t take any medications," he adds.

The study’s findings were that patients on no antiretrovirals or who had documented nonadherence lived an average of 126 days, those on mono- or dual therapy lived an average of 445 days, and those on HAART lived an average of 792 days.

There was one subgroup of PML/HIV patients included in the study who lived only 60 days despite receiving HAART. This group had been started on HAART too late, when the PML was at its peak according to symptoms, Neughebauer says. "Our suggestion is that if you have a patient who has a bit of confusion, an MRI should be done," he says. Also, clinicians should perform a polymerase chain reaction test to identify the JC virus.

HAART has no direct effect on the JC virus, but by suppressing HIV, it permits the patient’s immune system to fight the JC virus effectively, Neughebauer says.

Reference

1. Neughebauer BI, Kuhnert WL, Cohn SE. AIDS-associated progressive multifocal leukoencephalopathy (PML) in the pre- and post-HAART era. Abstract #373 presented at the Infectious Diseases Society of America conference. New Orleans; Sept. 7-10, 2000.