Antiretroviral Therapy May Induce Remission in PML
ABSTRACTS & COMMENTARY
Sources: Eliot B, et al. 2-5 year remission of AIDS-associated progressive multifocal leukoencephalopathy with combined antiretroviral therapy. Lancet 1997;349:850. Vollmer-Haase J, et al. Efficacy of camptothecin in progressive multifocal leucoencephalopathy. Lancet 1997;349:1366; Domingo, et al. Remission of progressive multifocal leucoencephalopathy after antiretroviral therapy. Lancet 1997;349:1554-1555; Baldeweg T, Catalan J. Editorial. Remission of progressive multifocal leukoencephalopahty after antiretroviral therapy. Lancet 1997;349:1555.
Progressive multifocal leukoencephalopathy (PML) is caused by human neurotropic virus (JC virus) in association with immune deficit, as caused by AIDS, anticancer drugs, immune suppression for organ transplants, and, rarely, idiopathic systemic autoimmune disorders such as lupus erythematosus. The disease is characteristically progressive and often fatal. Anecdotal reports, however, describe modest regression in a few patients treated with cytarabine, interferon, or zidovudine.
Against this gloomy background, four letters to The Lancet describe more hopeful outcomes associated with new or standard antiviral agents.
Eliot et al describe a two-and-a-half year remission in a 35-year-old man with AIDS who developed a progressive right hemiplesia with an associated dysarthria and aphasia. MRI scan identified a large high-signal lesion in the left corona radiata extending into the left internal capsule and corticospinal tract. He was treated with a combination of zidovudine 200 mg tid and didanosine 200 mg bid. Within four weeks, he could think and speak well and by week 12 could re-assume his job as a fisherman. The protease inhibitor indinavir (600 mg every 6 hours) was started at 24 weeks. By week 44, CD4 count rose to 230 cells/mcL, and the viral load was 240 copies/mL. MRI scan at 16 months showed two-thirds clearing of the PML abnormalities, and at two-and-a-half years he remained at 95% of his pre-PML state.
A less striking improvement marked a 32-year-old woman with lupus erythematosus, whose case was reported by Vollmer-Haase et al. Two episodes of renal failure were treated with cyclophosphamide, and she remained well for two-and-a-half years. At that point, she slowly developed over two months a left hemiplegia with aphasia-mutism. Bilateral hemispheric demyelination developed, and a biopsy diagnosed PML with PCR evidence of JC virus in the spinal fluid. Neurologic symptoms progressed, and she was treated with two cycles of camptothecin. She regained the ability to speak but did not further improve clinically.
Domingo et al describe a more favorable experience. A 68-year-old man with AIDS developed ataxia and hemiparesis with a normal mental status and a CD4 cell count of 58/mcL. MRI revealed PMA, and his initial viral load was 2.136 ´ 106 copies/mcL. After eight weeks of receiving stavudine, lamivudine, and indinavir, his well-being increased, he gained weight, the neurological abnormalities departed, and his viral load fell drastically. MRI, however, showed no changes from the pre-treatment images. Clinically, he remained well for at least eight months.
Finally, Baldeweg and Catalan, evaluating outcomes of 1109 AIDS patients, found that those treated with zidovudine had a reduced incidence of developing PML (relative risk 0.23 [95% CI 0.06-0.90]).
COMMENTARY
Four anecdotes do not a series make. Nevertheless, these letters describing improved PML after taking various but similar antiviral agents are encouraging. Eliot et al’s note is most upbeat and suggests that the inclusion of a protease inhibitor in the therapeutic cocktail may induce indefinitely prolonged improvement. fp
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