SURVIVAL PROLONGATION IN HIV-ASSOCIATED PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY TREATED WITH ALPHA-INTERFERON - AN OBSERVATIONAL STUDY

A retrospective chart review was conducted to determine the effect of alpha-Interferon (alpha-IFN) on disease progresssion, symptom palliati on, and survival in HIV-associated Progressive Multifocal Leukoencepha lopathy (PML). Methods: Subjects were HIV seropositive patients diagno sed with PML at the Johns Hopkins Hospital between 1985 and July of 19 86. Diagnostic criteria for PML included both clinical symptomatology and histologic or radiographic confirmation. All patients with concomi tant CNS infections were excluded. Patients receiving a mininum treatm ent 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 PAIL. Twenty-one patients had received open-labe l alpha alpha-IFN treatment in a non-randomized manner for at least 3 weeks, and 32 met criteria for inclusion in the untreated group as his torical controls. Deceased treated patients were comparable to decease d untreated patients with respect to age, gender, race, HIV risk facto rs, AIDS-defining illnesses, and CD4+ counts. CD4+ counts and use of a nti-retroviral medications within 6 months of PML onset were higher am ong those who were living at the time of the study. Results: Among dec eased patients, median survival of treated patients was 127.5 days lon ger than that of untreated patients (Chi-square=4.21, P=0.04). When li ving and deceased treated patients were combined, the median survival was 325 days (range 35-1634) versus 121 days (range 46-176) in untreat ed patients (Chi-square=13.47, P < 0.001). When survival times in untr eated patients were left-censored to account for possible survivorship bias in treated patients, survival in treated patients remained signi ficantly prolonged (325 days versus 175.5 days, Chi-square=4.65, P=0.0 3). In addition, use of alpha-IFN was associated with a significant de lay in the onset of memory loss (Chi-square=8.59, P < 0.01). Seven alp ha-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 t his was not always correlated with clinical remission. Four of 32 untr eated patients also reported transient symptomatic improvements. Concl usion: This open-label study suggests that alpha-IFN may delay progres sion, palliate symptoms, and significantly prolong survival in HIV-ass ociated PML, and we therefore suggest that a controlled clinical trial is warranted.