Low-dose intravitreal cidofovir (HPMPC) therapy of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome.
OBJECTIVE
The authors have shown that long-term treatment of cytomegalovirus (CMV) retinitis with 20-microgram intravitreal injections of cidofovir (HPMPC) is highly effective but may be associated with iritis and profound hypotony. They evaluated the efficacy and safety of 10-microgram intravitreal injections of cidofovir and made comparisons with their findings of 20-microgram injections.


METHODS
The current study was conducted as a nonrandomized consecutive case series at the AIDS Ocular Research Unit of the University of California at San Diego. Twenty-seven eyes of 18 patients were injected with 10 micrograms intravitreal cidofovir and had complete follow-up. These were compared with another consecutive series of 24 eyes of 17 patients injected with 20 micrograms of cidofovir.


METHODS
The main outcome in this study was the incidence of failure to respond to treatment with 10-microgram injections. The authors also compared the time to progression of CMV retinitis after the initial intravitreal injections of 10 micrograms and 20 micrograms of cidofovir. Secondary outcomes included incidence of iritis and changes in intraocular pressure (IOP) after cidofovir injections.


RESULTS
The median time to retinitis progression was 45 days after a single intravitreal injection of 10 micrograms cidofovir compared with 55 days with the authors' series of 20-microgram injections. This difference was statistically significant (P = 0.033, log-rank test) and appeared to be due principally to a 26% incidence of primary failure in the 10-microgram group (progression > or = 750 microns within 28 days, P = 0.0017 Wilcoxon test). Progression after a second injection of 10 micrograms cidofovir was more rapid (32 days, P = 0.037). The incidence of iritis after 10-microgram injections was 2.2% compared with 23% with 20-microgram injections (P = 0.003, Fisher's exact test, two-tailed). There was less decrease in IOP between the baseline injection and subsequent visits in the 10-microgram group.


CONCLUSIONS
Treatment of CMV retinitis with 10-microgram intravitreal cidofovir injection was not as effective as with 20 micrograms and may allow development of drug resistance, but there were fewer side effects with the 10-microgram dose. The drug appears to have a narrow therapeutic index, and other attempts at reducing the side effects while preserving the long-acting effect, such as liposome delivery, may be warranted.
Taskintuna
I
I
Department of Ophthalmology, Shiley Eye Center, University of California at San Diego, La Jolla 92093-0946, USA.
Rahhal
F M
FM
Arevalo
J F
JF
Munguia
D
D
Banker
A S
AS
De Clercq
E
E
Freeman
W R
WR
D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000077404:Cidofovir; D017726:Cytomegalovirus Retinitis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome; D014822:Vitreous Body
D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir