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

Abstract

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 followup 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 >or=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 1 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.

• Authors: Andrea De Luca, Adriana Ammassari, Patrizio Pezzotti, Paola Cinque, Jacques Gasnault, Juan Berenguer, Simona Di Giambenedetto, Antonella Cingolani, Yassine Taoufik, Pilar Miralles, Christina M Marra, Andrea Antinori, Gesida 9/99, IRINA, ACTG 363 Study Groups
• Journal: AIDS (London, England) (AIDS) Vol. 22 Issue 14 Pg. 1759-67 (Sep 12 2008) ISSN: 1473-5571 [Electronic] England
• PMID: 18753934 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Retroviral Agents
• Antiviral Agents
• Organophosphonates
• Cytosine
• Cidofovir

Topics

• AIDS-Related Opportunistic Infections (drug therapy)
• Adult
• Anti-Retroviral Agents (therapeutic use)
• Antiviral Agents (therapeutic use)
• Cidofovir
• Cohort Studies
• Cytosine (analogs & derivatives, therapeutic use)
• Female
• Humans
• Leukoencephalopathy, Progressive Multifocal (drug therapy)
• Male
• Morbidity
• Odds Ratio
• Organophosphonates (therapeutic use)
• Proportional Hazards Models
• Risk
• Survival Analysis
• Treatment Failure