A Study to Evaluate the Use of Cidofovir (an Experimental Drug) for the Treatment of Progressive Multifocal Leukoencephalopathy (PML) in AIDS Patients

A Pilot Study of the Effect of Cidofovir for the Treatment of Progressive Multifocal Leukoencephalopathy (PML) in Subjects With Acquired Immunodeficiency Syndrome (AIDS)

The purpose of this study is to evaluate the safety, tolerance, and overall effectiveness of cidovir to treat PML in AIDS patients.

PML is an opportunistic infection (HIV-associated, due to weak immune system) caused by a virus that attacks the brain. Cidovir has been used effectively to treat cytomegalovirus (CMV) of the eye. Cidovir could be an effective treatment for PML as well.

PML is a demyelinating disease of the brain's white matter, occurring when the JC virus infects the brain of patients infected with HIV-1. Cidofovir is known to be an effective treatment for cytomegalovirus of the eye and, in laboratory and animal testing, has also been shown to be effective against several other viruses. However, cidofovir is considered investigational as a treatment for PML.

In this multicenter, open-label study 24 patients receive cidofovir iv over 1 hr on days 0, 7, then every 2 wk for a total of 13 doses.

Oral probenecid is given 3h prior to and 2h and 8h following cidofovir administration. Nucleoside and non-nucleoside reverse transcriptors are withheld on days of probenecid administration. Protease inhibitors are continued during probenecid administration.

Inclusion Criteria

You may be eligible for this study if you:

• Are HIV-positive.
• Have had symptoms of PML for no more than 90 days before study entry, or have had abnormal neurological exams related to PML.
• Have negative tests for bacterial or fungal infections.
• Agree to practice abstinence or use effective methods of birth control during the study.
• Are at least 18 years old.
• Have a life expectancy of at least 6 months.

Exclusion Criteria

You will not be eligible for this study if you:

• Have a history of uveitis.
• Are allergic to sulfa drugs or probenecid.
• Have had active opportunistic infections other than Kaposi's sarcoma within 30 days before study entry.
• Have sickle cell anemia or trait.
• Are pregnant or breast-feeding.