Survival prolongation in HIV-associated progressive multifocal leukoencephalopathy treated with alpha-Interferon: an observational study

Abstract

A retrospective chart review was conducted to determine the effect of alpha-Interferon (alpha-IFN) on disease progression, symptom palliation, and survival in HIV-associated Progressive Multifocal Leukoencephalopathy (PML). Subjects were HIV seropositive patients diagnosed with PML at the Johns Hopkins Hospital between 1985 and July of 1986. Diagnostic criteria for PML included both clinical symptomatology and histologic or radiographic confirmation. All patients with concomitant CNS infections were excluded. Patients receiving a minimum treatment of 3 weeks of 3 million units of alpha-IFN daily were compared to untreated historical controls. From 104 PML cases reviewed, 77 met the defined criteria for PML. Twenty-one patients had received open-label alpha-IFN treatment in a non-randomized manner for at least 3 weeks, and 32 met criteria for inclusion in the untreated group as historical controls. Deceased treated patients were comparable to deceased untreated patients with respect to age, gender, race, HIV risk factors, AIDS-defining illnesses, and CD4+ counts. CD4+ counts and use of anti-retroviral medications within 6 months of PML onset were higher among those who were living at the time of the study. Among deceased patients, median survival of treated patients was 127.5 days longer than that of untreated patients (Chi-square=4.21, P=0.04). When living and deceased treated patients were combined, the median survival was 325 days (range 35 - 1634) versus 121 days (range 46 - 176) in untreated patients (Chi-square=13.47, P < 0.001). When survival times in untreated patients were left-censored to account for possible survivorship bias in treated patients, survival in treated patients remained significantly prolonged (325 days versus 175.5 days, Chi-square=4.65, P=0.03). In addition, use of alpha-IFN was associated with a significant delay in the onset of memory loss (Chi-square=8.59, P < 0.01). Seven alpha-IFN treated patients showed sustained remissions of several months to over a year, with documented improvements in mental status, aphasia, dysarthria, dysphagia, paresis, and dyscoordination. Moreover, four IFN-treated patients had evidence of MRI lesion regression, although this was not always correlated with clinical remission. Four of 32 untreated patients also reported transient symptomatic improvements. This open-label study suggests that alpha-IFN may delay progression, palliate symptoms, and significantly prolong survival in HIV-associated PML, and we therefore suggest that a controlled clinical trial is warranted.