AIDS Guide for Health Care Workers
AIDS Guide for Health Care Workers
HIV patients who have PML can now live for years
Patients will live longer with PML if they are diagnosed and treated early
Before the introduction of antiretroviral treatment and combination therapies containing protease inhibitors and other powerful HIV medications, AIDS patients who developed progressive multifocal leukoencephalopathy (PML) typically would die within three to six months.
This severe neurologic disease progressed rapidly in AIDS patients, causing muscle weakness; spasms; blurred or double vision; difficulty with walking, swallowing, and speaking; headaches; confusion; poor concentration; and sometimes blindness.
Recent studies suggest that some HIV patients who are diagnosed with PML early in the disease have survived for more than three years while receiving combination antiretroviral therapy. However, at least one study has found that the survival rate is greatest when the patients are not in advanced stages of HIV disease and PML disease. This is why it's very important for clinicians to diagnose PML as early as possible.
Here is some information about PML, its diagnosis, and its treatment:
• What is progressive multifocal leukoencephalopathy?
This rare AIDS-related condition is caused by the JC virus, which is a polyomavirus of the papovavirus family. The JC virus is believed to have infected up to 90% of adults, so infection cannot be prevented. However, it only develops into a fatal demyelinating disease of the brain in people who are severely immunocompromised.
A chronic progressive illness, PML causes patients to decline rapidly, usually resulting in dementia, encephalopathy, coma, and death.
Most cases of PML occur in people with AIDS whose CD4+ cell counts are very low, such as people with CD4 counts of less than 90 cells/mm3.
In PML, the JC virus infects the brain, forming lesions. There is no standard course of the disease because there's no way to predict which part of the brain the virus will strike first. For instance, if the virus first infects the part of the brain that controls speech, the first sign of PML disease in that patient would be aphasia. But in another person, the virus could first infect the part of the brain that affects eyesight, so that person's first symptom would be a change in vision.
• What are PML’s symptoms and how is it diagnosed?
Symptoms include muscle incoordination, cranial nerve deficits, cortical blindness, gait abnormalities, personality changes, fever, confusion, paralysis on one side, and speech difficulties.
PML cannot be diagnosed solely by symptoms or by a magnetic resonance imaging (MRI) brain scan, because other AIDS-related opportunistic infections present similar symptoms and MRI results, such as toxoplasmosis, AIDS dementia complex, lymphoma, cytomegalovirus, herpes infections, and cryptococcal meningitis. Because a majority of adults have antibodies to the JC virus, it’s also not useful to conduct blood or urine tests as a diagnostic tool.
Clinicians may suspect PML when a computed tomography (CT) or MRI scan shows multiple areas of cerebral white matter demyelination. But a more specific diagnosis requires a biopsy of brain tissue.
There is new research suggesting that a polymerase chain reaction (PCR) analysis of cerebrospinal fluid will enable a diagnosis of the disease in a majority of cases. But clinicians now are using PCR testing in conjunction with a brain biopsy.
Patients may be reluctant to have a brain biopsy because of the procedure’s invasiveness. However, if PML is suspected, the biopsy is recommended, because it can rule out other common brain diseases that may be treatable.
• How is PML treated?
Until recently, there were no effective treatments, and patients who had this illness could expect to die very soon after diagnosis. This dismal prognosis has changed since the introduction of protease inhibitors and combination antiretroviral therapies for HIV patients.
The key to preventing the JC virus from infecting the brain — or, once it has infected the brain, from progressing rapidly — appears to be to keep the HIV-infected person’s immune system as strong as possible. New research suggests that HIV patients who have healthy immune systems and are on antiretroviral therapy do not develop PML.
Some experts recommend treating PML specifically by using antiretroviral drugs that cross the blood-brain barrier. These include AZT, stavudine, didanosine, zalcitidabine, lamivudine, nevirapine, and amprenavir.
Medical experts also recommend that clinicians use MRI to monitor changes in the size of PML lesions during a course of treatment.
There also is a controversial and toxic drug called cytosine arabinoside, often used as chemotherapy for leukemia and cancer, that can be used to treat PML. Clinicians administer the drug by placing a shunt into the patient’s brain or vein and delivering the drug directly.
The drug’s possible side effects are nausea, bone marrow toxicity, and fevers. Prednisone and granulocyte colony-stimulating factor (G-CSF) may be administered to help reduce side effects. The other problem with cytosine arabinoside is that its results have been mixed in clinical studies. Some research has shown it to have no benefit.
Researchers also are investigating the use of cidofovir for treating PML. This drug must be injected intravenously and must be given with probenecid to reduce the risk of kidney toxicities. But the drug is still being studied and it has many side effects, so it is a long way from being of value in treating PML.
• What are the sources of information for the material presented here?
Lemens G. "PML Treatment." Treatment Issues. Gay Men’s Health Crisis, Inc. 1992. New York; 6:5-7.
McGuire D, So YT. "Progressive Multifocal Leukoencephalopathy." The Nervous System in HIV and AIDS. hivinsite.ucsf.edu/akb/1997/ 05neuro/index.html. June 1998.
"Progressive Multifocal Leukoencephalopathy (PML)." Project Inform. www.projinf.org/fs/pml.html. September 2000.
Cinque P, Casari S. Progressive multifocal leukoencephalopathy, HIV, and highly active antiretroviral therapy (letter). N Engl J Med 1998; 339:848-849.
Greenlee JE. Progressive multifocal leukoencephalopathy — progress made and lessons relearned (editorial). N Engl J Med 1998; 338:1378-1380.
Hall CD, et al and the AIDS Clinical Trials Group. Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. N Engl J Med 1998; 338:1345-1351.
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.
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