What's New in Treatment Information?
Excerpts from Hotline Memos of August 2000
from the Information Department of Project Inform
Cidofovir and Progressive Multifocal Leukoencephalopathy (PML)Results from an Italian study suggest that cidofovir (Vistide) may be useful for people with progressive multifocal leukoencephalopathy (PML). PML is a relatively rare disease in people living with HIV, affecting the brain. It is caused by a virus, called the JC virus. Most adults (about 80%) are exposed to this virus but it usually only causes disease in people with very low CD4+ cell counts. In rare circumstances, PML can occur in people with higher CD4+ cell counts (e.g., above 200).
PML is an aggressive disease. Historically, the average time from PML diagnosis to death was about 90 days. Since the availability and use of potent anti-HIV therapies, however, survival time after a diagnosis with PML has extended significantly, with a number of people having post-PML diagnosis survival of two to five years (and counting!).
Because PML affects the brain, diagnosing the disease is difficult and oftentimes it is diagnosed presumptively (i.e., based on symptoms and not definitive laboratory tests, which would include a brain biopsy). Treatments for PML are, at best, rather ineffective. The typical approach to treatment, when treatment is pursued, is ARA-C, which has many side effects and is delivered through a shunt directly into the brain. Because of the invasiveness of treatment, many people choose not to treat PML with ARA-C. With the advent of potent anti-HIV therapies, the incidence of PML has decreased dramatically.
The most recent study involved 40 people with PML all of whom were taking potent anti-HIV therapy but only fourteen of the individuals were also taking cidofovir, a drug approved for the treatment of cytomegalovirus (CMV). The dose of cidofovir used in this study was 5mg/kg every week for the first two weeks then 5mg/kg every other week. People receiving cidofovir had better responses; a more pronounced increase in CD4+ cell counts and prolonged survival compared to people receiving only potent anti-HIV therapy.
Further analysis of the results show that the following factors led to prolonged survival: use of cidofovir, lower JC virus levels at the start of the study and starting potent anti-HIV therapy prior to developing PML.
Cidofovir is a very difficult drug to take. It has to be given by injection directly into the vein (intravenously) and has to be given with probenecid to reduce the risk of developing kidney toxicities. However, even with the use of probenecid, a fair number of people have problems tolerating the drug.
CommentaryWhile there are no standard of care guidelines for PML, this study suggests that the addition of cidofovir to potent anti-HIV therapy should be considered. However, the side effect profile for cidofovir is still of great concern.
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