Cidofovir in addition to antiretroviral treatment is not effective for AIDS-associated progressive multifocal leukoencephalopathy: a multicohort analysis

被引:105
作者
De Luca, Andrea [1 ]
Ammassari, Adriana [2 ]
Pezzotti, Patrizio [3 ]
Cinque, Paola [4 ]
Gasnault, Jacques [5 ]
Berenguer, Juan [6 ]
Di Giambenedetto, Simona [1 ]
Cingolani, Antonella [1 ]
Taoufik, Yassine [7 ]
Miralles, Pilar [6 ]
Marra, Christina M. [8 ]
Antinori, Andrea [2 ]
机构
[1] Univ Cattolica Sacro Cuore, Ist Clin Malattie Infett, I-00168 Rome, Italy
[2] IRCCS, Natl Inst Infect Dis Lspallanzani, Rome, Italy
[3] Agcy Publ Hlth, Rome, Italy
[4] Ist Sci San Raffaele, Infect Dis Unit, I-20132 Milan, Italy
[5] Bicetre Univ Hosp, Dept Internal Med, NeuroAIDS Rehabil Unit, Le Kremlin Bicetre, France
[6] Hosp Gen Gregorio Maranon, Unidad Enfermedades Infecc, Madrid, Spain
[7] Bicetre Univ Hosp, Immunol Lab, Le Kremlin Bicetre, France
[8] Univ Washington, Sch Med, Dept Neurol & Med, Seattle, WA 98195 USA
关键词
cidofovir; combination antiretroviral therapy; JC virus; progressive multifocal leukoencephalopathy;
D O I
10.1097/QAD.0b013e32830a5043
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 establish the effectiveness of cidofovir for AIDS-related progressive multifocal leukoencephalopathy (PML) in patients concomitantly receiving combination antiretroviral therapy. Design: Analysis of raw data pooled from one prospective and five cohort studies. Setting: Tertiary care centers for the treatment of HIV-associated complications. Patients: Three hundred seventy HIV-infected PML patients diagnosed from 1996 treated with combination antiretroviral therapy with or without cidofovir. All studies had already published their results but for four of them, additional patients and follow-up data are included in this report. Follow-up was started from the date of first abnormal neuroimaging; those treated with cidofovir were entered at risk at the date of cidofovir initiation. Main Study outcomes were time to PML-related death and odds of 12-month moderately severe to severe disability (Rankin score >= 4). Results: Sixty-four percent of the PML cases were confirmed by histopathology or JC virus DNA detection in cerebrospinal fluid; 185 (50%) received cidofovir (median five cycles). During 463 person-years of follow-up, 167 PML-related deaths occurred (36.6 per 100 person-years of follow-up). Estimated I year survival was 0.56 (95% confidence interval, 0.50-0.61). In multivariate models stratified by cohort and adjusted for type of diagnosis and relevant prognostic confounders, cidofovir treatment was not associated with survival (hazard ratio for death 0.93, 0.66-1.32). Results were similar using time to death from any cause as the outcome. Furthermore, 12-month moderately severe to severe disability was not associated with the use of cidofovir. Conclusion: In combination antiretroviral therapy-treated PML patients, cidofovir use did not influence PML-related mortality or residual disability. New treatments for AIDS-related PML are urgently needed. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
引用
收藏
页码:1759 / 1767
页数:9
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