A pilot study of cidofovir for progressive multifocal leukoencephalopathy in AIDS

被引:136
作者
Marra, CM
Rajicic, N
Barker, DE
Cohen, BA
Clifford, D
Post, MJD
Ruiz, A
Bowen, BC
Huang, ML
Queen-Baker, J
Andersen, J
Kelly, S
Shriver, S
机构
[1] Univ Washington, Harborview Med Ctr, Dept Neurol & Med, Sch Med, Seattle, WA 98104 USA
[2] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA
[3] Rush Med Coll, Cook Cty Hosp, CORE Ctr, Chicago, IL 60612 USA
[4] Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA
[5] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
[6] Univ Miami, Sch Med, Dept Radiol, Miami, FL USA
[7] Univ Washington, Fred Hutchinson Canc Res Ctr, Program Infect Dis, Div Virol, Seattle, WA 98195 USA
[8] Social & Sci Syst Inc, Adult AIDS Clin Trials Grp, Bethesda, MD 20814 USA
关键词
cidofovir; HIV; JC virus; magnetic resonance imaging; neurological examination; polymerase chain reaction; progressive multifocal leukoencephalopathy;
D O I
10.1097/00002030-200209060-00012
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective: To assess the safety, tolerability and effect of cidofovir for HIV-1 associated progressive multifocal leukoencephalopathy. Design: Prospective, open-label study in nine AIDS Clinical Trials Units. Patients and methods: Twenty-four HIV-1-infected individuals, with neuroimaging and clinical findings consistent with PML, and symptoms for 90 days or less, whose diagnosis was confirmed by the detection of JC virus DNA in the cerebrospinal fluid or brain biopsy received cidofovir 5 mg/kg intravenously at baseline and I week, followed by infusions every 2 weeks with the dose adjusted for renal function. Followup continued to 24 weeks. The safety of cidofovir and changes in neurological examination scores between baseline and week 8 were assessed. Results: Seventeen subjects were receiving potent antiretroviral agents. Survival at 12 weeks was 54%. The CD4 cell count at entry was significantly associated with survival (P=0.02). Five subjects discontinued treatment because of toxicity: a 50% or greater decrease in intraocular pressure in either eye in four, and proteinuria in one. Overall, magnetic resonance imaging abnormalities and neurological examination scores worsened. Only two subjects experienced a 25% or greater improvement in neurological examination scores at week 8, which were significantly better in subjects with HIV-1-RNA levels of 500 copies/ml or less at entry compared with those with HIV-1-RNA levels over 500 copies/ml (P=0.05). Conclusion: Cidofovir did not improve neurological examination scores at week 8. However, such scores were significantly better in subjects who entered with suppressed plasma HIV-1-RNA levels, which could be the result of control of HIV-1 infection itself or cidofovir. (C) 2002 Lippincott Williams Wilkins.
引用
收藏
页码:1791 / 1797
页数:7
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