Objectives: To analyse the virological and clinical efficacy of cidofovir c
ombined with highly active antiretroviral therapy (HAART) in AIDS-related p
rogressive multifocal leukoencephalopathy (PML).
Design: Multicentre observational study of consecutive HIV-positive patient
s with histologically or virologically-proven PML. Group A, 26 patients tre
ated with HAART; group B, 14 patients treated with HAART plus cidofovir 5 m
g/kg intravenously per week for the first 2 weeks and alternate weeks there
after. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR.
Results: Baseline virological, immunological and clinical characteristics w
ere homogeneous between the groups. In one case cidofovir was discontinued
because of severe proteinuria. There was no significant difference in HIV R
NA responses and changes in the number of CD4 cells between group A and B.
After 2 months of therapy, five out of 12 (42%) patients from group A and s
even out of eight (87%) from group B reached undetectable JC virus DNA in t
he CSF (Chi-square P = 0.04); moreover, 24% of group A and 57% of group B p
atients showed neurological improvement or stability (P = 0.038). One-year
cumulative probability of survival was 0.67 with cidofovir and 0.31 without
(log-rank test, P = 0.01). Variables independently associated with longer
survival were the use of cidofovir, HAART prior to the onset of PML, a base
line JC virus DNA load in CSF < 4.7 log(10) copies/ml, and a baseline Karno
fsky performance status <greater than or equal to> 60.
Conclusions: In AIDS-related PML, cidofovir added to HAART is associated wi
th a more effective control of ICV replication, with improved neurological
outcome and survival compared with HAART alone. (C) 2000 Lippincott William
s & Wilkins.