title: Potent anti-retroviral therapy with or without cidofovir for AIDS-associated progressive multifocal leukoencephalopathy: extended follow-up of an observational study.
abstract: To analyze the clinical efficacy of cidofovir combined with highly active anti-retroviral 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.
authors.affiliation: Department of Clinical Infectious Diseases, Università Cattolica del S Cuore, Rome, Italy. andeluc@tin.it
authors.forename: A
authors.initials: A
authors.lastname: De Luca
authors.forename: M L
authors.initials: ML
authors.lastname: Giancola
authors.forename: A
authors.initials: A
authors.lastname: Ammassari
authors.forename: S
authors.initials: S
authors.lastname: Grisetti
authors.forename: A
authors.initials: A
authors.lastname: Cingolani
authors.forename: D
authors.initials: D
authors.lastname: Larussa
authors.forename: L
authors.initials: L
authors.lastname: Alba
authors.forename: R
authors.initials: R
authors.lastname: Murri
authors.forename: G
authors.initials: G
authors.lastname: Ippolito
authors.forename: R
authors.initials: R
authors.lastname: Cauda
authors.forename: A
authors.initials: A
authors.lastname: Monforte
authors.forename: A
authors.initials: A
authors.lastname: Antinori
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000401:mortality; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000008:administration & dosage*; D000077404:Cidofovir; D003596:Cytosine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage*; D015996:Survival Rate
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir