Incidence and Outcome of Progressive Multifocal Leukoencephalopathy over 20 Years of the Swiss HIV Cohort Study
Khanna N, et al. Clin Infect Dis 2009;48:1459-1466. [PubMed Abstract]

Background: Progressive Multifocal Leukoencephalopathy (PML) is a rare but often rapidly fatal complication of HIV infection.  In the pre-HAART era, the prevalence among persons with HIV infection was reported at 0.3-0.8% and the survival for 1 year was less than 10% (Ann Intern Med 1987;107:78; Ann Neurol 1991;30:597; Pathol Res Pract 1995;191:427).  The more recent studies show a much higher survival rate but high rates of severe neurologic disease in most of the survivors (AIDS 2008;22:1759; CID 2003;36:1047).

Purpose:  To determine the incidence and outcome of PML in patients with HIV infection before and after HAART.

Methods:  The review is based on 186 cases of PML reported to the Swiss HIV Cohort Study from 1988 through 2007. 

Results:  Diagnosis:  The diagnosis of PML was based on clinical and neuroradiologic findings in 95 patients (60%); there was laboratory confirmation with JC viral DNA in CSF in 38 patients (24%), and diagnosis by histologic exam of a brain biopsy or autopsy in 26 patients (16%).  PCR for JC was done in 81 patients and JC virus was detected in 40 (50%) of these.

Patient characteristics:  Comparison of patients in the pre- and post-HAART era showed similar results for age, and baseline VL and CD4 cell count.  Remarkable differences were noted in incidence.  These data are shown in the following Table:

*Authors conclude immune reconstitution inflammatory syndrome (IRIS) was underreported.

Outcome:  Within 1 year of diagnosis, 97 (61%) patients died.  The median survival time was 90 days.  The deaths were attributed to PML in 51 (53%) giving a 1-year mortality of 60 deaths per 100 person-years (PY).  The median time from diagnosis to death attributed to PML was 71 days.  Long-term follow-up of patients who survived >1 year was available for 47 patients, of whom 39 (83%) had persistent neurological deficits and 8 (17%) showed clinical improvement.  With regard to the two periods of study, the 1-year survival was substantially better in the HAART era with 38 deaths per 100 patient years compared to 82 in the pre-HAART (Table above).

Conclusion:  The authors conclude that HAART has been responsible for a 4-fold decrease in the rate of PML and a 2-fold reduction in the 1-year mortality in those who developed this complication.

Comment:  PML continues to be a devastating complication of HIV infection for which there is no specific therapy, and a poor prognosis for survival and neurologic recovery in those who do survive.  This report of 159 cases is possibly the largest and is a reflection of what others have reported in smaller series.  Of note, the sensitivity of PCR with CSF for JC virus seemed relatively low in this series (50%) because the sensitivity generally reported is 70-90% (AIDS 1997;11:1; Clin Microbiol Infect 1998;4:577).  Nevertheless, a more recent report suggests reduced sensitivity in patients receiving HAART with relatively high CD4 cell counts (J Clin Microbiol 2005;43:4175).