Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS.
To assess the effect of intravenous cidofovir on delaying progression of previously treated, relapsing cytomegalovirus (CMV) retinitis, we conducted a randomized, controlled comparison of two maintenance dose levels of cidofovir. One hundred and fifty patients with AIDS and CMV retinitis that had progressed or was persistently active despite treatment with ganciclovir, foscarnet, or both were randomized to receive induction cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with either 5 mg/kg or 3 mg/kg once every other week. Concomitant probenecid and intravenous hydration were administered with each cidofovir dose. Retinitis progression was assessed in the first 100 patients by bilateral, full-field retinal photographs read at a central reading center by an ophthalmologist masked to treatment assignment. Incidence of side effects, changes in visual acuity, and mortality were also assessed. Median time to retinitis progression as assessed by retinal photography was not reached (95% confidence interval [CI], 115 days-upper limit not reached) in the 5-mg/kg group, and was 49 days (95% CI, 35-52 days) in the 3-mg/kg group (p = .0006). Dose-dependent asymptomatic proteinuria (39%) and serum creatinine elevation (24%) were the most common adverse events thought to be related to cidofovir. Reversible probenecid reactions including constitutional symptoms and nausea occurred in 65 of 150 (43%) patients. Cidofovir therapy is effective in delaying progression of CMV retinitis that had previously progressed using other anti-CMV therapies.
Lalezari
J P
JP
University of California, San Francisco-Mt. Zion Medical Center, USA.
Holland
G N
GN
Kramer
F
F
McKinley
G F
GF
Kemper
C A
CA
Ives
D V
DV
Nelson
R
R
Hardy
W D
WD
Kuppermann
B D
BD
Northfelt
D W
DW
Youle
M
M
Johnson
M
M
Lewis
R A
RA
Weinberg
D V
DV
Simon
G L
GL
Wolitz
R A
RA
Ruby
A E
AE
Stagg
R J
RJ
Jaffe
H S
HS
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077404:Cidofovir; D003404:Creatinine / Q000097:blood; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy*; D003596:Cytosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007429:Intraocular Pressure / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011339:Probenecid / Q000009:adverse effects / Q000627:therapeutic use; D011507:Proteinuria / Q000139:chemically induced; D012008:Recurrence; D012076:Renal Agents / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D014792:Visual Acuity
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D012076:Renal Agents; D003596:Cytosine; D003404:Creatinine; D000077404:Cidofovir; D011339:Probenecid