2·5 year remission of AIDS-associated progressive multifocal leukoencephalopathy with combined antiretroviral therapy

Progressive multifocal leukoencephalopathy (PML) results from infection of the central nervous system with JC virus, a papovavirus, which causes demyelination in the white matter of the brain. Long-term survival in AIDS patients with PML is rare. There is no consistently effective treatment although cytarabine, interferon, and zidovudine (AZT) may occasionally result in regression. We report remission of PML-associated hemiparesis for 104 weeks during combination antiretroviral therapy including a protease inhibitor. A 35-year-old man and previous intravenous drug user, was admitted due to worsening neurological symptoms, including dysarthria, aphasia, a right-sided facial droop, right arm weakness, and a walk that listed to the right. A T2weighted MRI scan showed confluent high signal intensity in the left centrum semiovale, left corona radiata with extension into the left internal capsule, left cerebral peduncle, and the pontine cortical spinal tracts (left figure). There was faint enhancement without mass effect. The MRI findings were characteristic of those observed with PML. No brain biopsy was done. Laboratory studies (ELISA and western blot) established the diagnosis of HIV infection. The CD4 count was 30 cells/μL and his HIV viral load was 189 900 copies/mL. He began zidovudine 200 mg three times daily and didanosine 200 mg twice daily as part of a controlled trial. Over the next 2–4 weeks the patient’s ability to convey thoughts quickly and to speak clearly improved. By the 10th week of antiretroviral therapy, he began an exercise regimen which included weight-lifting and aerobic activity and, by week 12, he was able to return to work as a fisherman. At week 24, indinavir, a protease inhibitor, was added (600 mg every 6 hours) to the anti-HIV regimen. By week 44, the CD4 count had increased to 230 cells/μL and the viral load was 240 copies/mL. A repeat MRI scan, 16 months after the first, demonstrated improvement in the extent of the T2 abnormalities (right figure). In none of the reported cases of long-term survival of patients treated with zidovudine or cytarabine was the remission as complete as the one cited here, although, since a biopsy was not done, it is possible that the initial presentation of aphasia and right arm weakness was not due to PML, but to an unusual manifestation of HIV. In previously reported cases, either the original symptoms were less severe or the resolution of neurological deficits was not as complete. Our patient has survived beyond the mean (over 2 years from the onset of symptoms) and has regained over 95% of his original function. This remission has been associated with improvement in immune function, evident by the rise in CD4 count. As more effective antiretroviral regimens become available, there may be more frequent remissions in persons with PML.