Cidofovir added to HAART improves virological and clinical outcome in AIDS-associated progressive multifocal leukoencephalopathy

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.