A pilot study of cidofovir for progressive multifocal leukoencephalopathy in AIDS.
OBJECTIVE
To assess the safety, tolerability and effect of cidofovir for HIV-1 associated progressive multifocal leukoencephalopathy.


METHODS
Prospective, open-label study in nine AIDS Clinical Trials Units.


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 1 week, followed by infusions every 2 weeks with the dose adjusted for renal function. Follow-up 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).


CONCLUSIONS
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.
Marra
Christina M
CM
Department of Neurology and Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Rajicic
Natasa
N
Barker
David E
DE
Cohen
Bruce A
BA
Clifford
David
D
Donovan Post
M Judith
MJ
Ruiz
Armando
A
Bowen
Brian C
BC
Huang
Meei-Li
ML
Queen-Baker
Jennie
J
Andersen
Janet
J
Kelly
Sue
S
Shriver
Sharon
S
D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001921:Brain / Q000821:virology; D002555:Cerebrospinal Fluid / Q000821:virology; D000077404:Cidofovir; D003596:Cytosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000302:isolation & purification; D007968:Leukoencephalopathy, Progressive Multifocal / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir