TY - JOUR
T1 - A pilot study of cidofovir for progressive multifocal leukoencephalopathy in AIDS
AU - Marra, Christina M.
AU - Rajicic, Natasa
AU - Barker, David E.
AU - Cohen, Bruce A.
AU - Clifford, David
AU - Donovan Post, M. Judith
AU - Ruiz, Armando
AU - Bowen, Brian C.
AU - Huang, Meei Li
AU - Queen-Baker, Jennie
AU - Andersen, Janet
AU - Kelly, Sue
AU - Shriver, Sharon
PY - 2002/9/6
Y1 - 2002/9/6
N2 - 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 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). 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.
AB - 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 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). 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.
KW - Cidofovir
KW - HIV
KW - JC virus
KW - Magnetic resonance imaging
KW - Neurological examination
KW - Polymerase chain reaction
KW - Progressive multifocal leukoencephalopathy
UR - http://www.scopus.com/inward/record.url?scp=18644377201&partnerID=8YFLogxK
U2 - 10.1097/00002030-200209060-00012
DO - 10.1097/00002030-200209060-00012
M3 - Article
C2 - 12218391
AN - SCOPUS:18644377201
SN - 0269-9370
VL - 16
SP - 1791
EP - 1797
JO - AIDS
JF - AIDS
IS - 13
ER -