Potent anti-retroviral therapy with or without cidofovir for AIDS-associated progressive multifocal leukoencephalopathy: Extended follow-up of an observational study

To analyze the clinical efficacy of cidofovir combined with highly active antiretroviral therapy (HAART) in AIDS-related progressive multifocal leukoencepalopathy (PML), a multicenter observational study was performed. Consecutive HIV-positive patients with histologically or virologically proven PML...

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Published in:Journal of neurovirology 2001-08, Vol.7 (4), p.364-368
Main Author: De Luca, Maria Letizia Giancola, Adriana Ammassari, Susanna Grisetti, Antonella Cingolani, Dora Larussa, Lucia Alba, Rita Murri, Giuseppe Ippolito, Roberto Cauda, Antonella d'Arminio Monforte, Andrea Antinori, Andrea
Format: Article
Language:English
Subjects:
Acquired Immunodeficiency Syndrome - drug therapy
Adult
AIDS-Related Opportunistic Infections - drug therapy
AIDS-Related Opportunistic Infections - mortality
Antiretroviral Therapy, Highly Active
Antiviral Agents - administration & dosage
cidofovir
Cytosine - administration & dosage
Cytosine - analogs & derivatives
Drug Therapy, Combination
Female
Follow-Up Studies
Human immunodeficiency virus
Humans
JC virus
leukoencephalopathy
Leukoencephalopathy, Progressive Multifocal - drug therapy
Leukoencephalopathy, Progressive Multifocal - mortality
Male
Middle Aged
Organophosphonates
Organophosphorus Compounds - administration & dosage
progressive multifocal leukoencepalopathy
Survival Rate
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Summary:To analyze the clinical efficacy of cidofovir combined with highly active antiretroviral therapy (HAART) in AIDS-related progressive multifocal leukoencepalopathy (PML), a multicenter observational study was performed. Consecutive HIV-positive patients with histologically or virologically proven PML and at least 4 weeks of treatment after diagnosis were examined: 27 patients were treated with HAART, whereas 16 patients were treated with HAART plus cidofovir 5 mg/kg intravenously per week for the first 2 weeks and every other week thereafter. JC virus DNA was quantified in cerebrospinal fluid (CSF) by PCR. Baseline virologic, immunologic, and clinical characteristics as well as HIV RNA and CD4 responses to HAART were homogeneous between the groups. The median follow-up was 132 weeks. In one case (6%), cidofovir was permanently discontinued because of severe proteinuria. One-year cumulative probability of survival was 0.61 with cidofovir and 0.29 without (log rank test P = 0.02). After adjusting for baseline CD4 counts, JC viral load in CSF, Karnofsky,and use of HAART prior to the onset of PML, the use of cidofovir was independently associated with a reduced risk of death (hazard ratio, 0.21, 95% confidence interval, 0.07-0.65; P = 0.005). A randomized study will definitively establish whether cidofovir confers significant advantage over HAART alone in AIDS-related PML. Journal of NeuroVirology (2001) 7, 364-368.
ISSN:1355-0284
1538-2443
DOI:10.1080/13550280152537256