Progressive multifocal leukencephalopathy in patients on highly active antiretroviral therapy: survival and risk factors of death.
OBJECTIVE
To describe the clinical course and risk factors of death in highly active antiretroviral therapy (HAART)-treated patients with progressive multifocal leukencephalopathy (PML); to evaluate the efficacy of cidofovir in addition to HAART.


METHODS
Retrospective multicenter cohort study of PML in HIV-1-infected patients. Diagnosis of PML was confirmed by histology or by positive polymerase chain reaction for JC virus (JCV) in cerebrospinal fluid (CSF) or was made by typical radiologic and clinical findings.


RESULTS
Thirty-five cases of PML were identified. The diagnosis was made by histology (9 cases), detection of JCV in CSF (17 cases), and by radiologic findings (9 cases). Upon manifestation of PML, 15/35 patients had never received HAART, and 11/35 were on HAART for >6 months (median 1126 days). In 9/35 cases, clinical manifestation of PML occurred within 6 months after initiation of HAART. All patients received HAART after PML diagnosis. After a median follow-up of 553 days (range 28-2694 days), the median survival time was not reached. In 12 patients who were treated concomitantly with cidofovir, cumulative survival was significantly shorter than in patients without cidofovir (P = 0.03). Patients in whom PML was diagnosed while on HAART demonstrated a trend toward a shorter survival than HAART-naive patients (P = 0.15).


CONCLUSIONS
PML continues to occur in HIV-1-infected patients even when they are treated with HAART. Patients developing PML on HAART had a trend toward a shorter median survival compared with treatment-naive patients, and cidofovir therapy was not associated with improved survival in this cohort.
Wyen
Christoph
C
Klinik I für Innere Medizin, University of Cologne, Cologne, Germany. christoph.wyen@medizin.uni-koeln.de
Hoffmann
Christian
C
Schmeisser
Norbert
N
Wöhrmann
Andrej
A
Qurishi
Nazifa
N
Rockstroh
Jürgen
J
Esser
Stefan
S
Rieke
Ansgar
A
Ross
Birgit
B
Lorenzen
Thore
T
Schmitz
Karina
K
Stenzel
Werner
W
Salzberger
Bernd
B
Fätkenheuer
Gerd
G
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D000077404:Cidofovir; D015331:Cohort Studies; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007577:JC Virus / Q000302:isolation & purification; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir