Pathophysiology and treatment of clinically resistant cytomegalovirus retinitis.
OBJECTIVE
To determine the incidence, pathophysiology, clinical outcome, and survival in patients with clinically resistant retinitis.


METHODS
Cytomegalovirus (CMV) retinitis was prospectively studied in 100 patients with acquired immune deficiency syndrome (AIDS). In 11 of these patients, clinically resistant retinitis developed, defined as new activity or progression, despite at least 8 consecutive weeks of induction doses of either foscarnet or ganciclovir. Fundus photography, pharmacokinetics, CMV cultures and sensitivities, and survival analyses were studied. The therapeutic interventions attempted after clinically resistant retinitis was identified included continuing a high dose (induction level) of the same antiviral drug, changing the antiviral drug, and combining antiviral therapy with foscarnet and ganciclovir.


RESULTS
Clinically resistant retinitis occurred in 11 (11%) of 100 patients with CMV retinitis and appeared to be a manifestation of acquired CMV antiviral drug resistance. Drug metabolism and pharmacokinetics in these patients were normal. The use of combination therapy with foscarnet and ganciclovir was effective in halting the progression of retinitis in three (75%) of four patients (6 of 7 eyes able to be evaluated) receiving combination therapy.


CONCLUSIONS
Clinically resistant retinitis is a manifestation of infection by CMV that has acquired drug resistance. In these patients, combination antiviral drug treatment should be considered. It is likely that clinically resistant retinitis will become more frequent as patients with CMV retinitis and AIDS survive longer.
Department of Ophthalmology, University of California San Diego, School of Medicine.
M
M
Flores-Aguilar
B D
BD
Kuppermann
J I
JI
Quiceno
W M
WM
Dankner
D G
DG
Wolf
E V
EV
Capparelli
J D
JD
Connor
C H
CH
Sherwood
S
S
Fullerton
J G
JG
Gambertoglio
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000503:physiopathology; D000328:Adult; D003587:Cytomegalovirus / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000503:physiopathology; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D015828:Eye Infections, Viral / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D017245:Foscarnet / Q000493:pharmacokinetics / Q000627:therapeutic use; D005654:Fundus Oculi; D015774:Ganciclovir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D012173:Retinitis / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D015996:Survival Rate; D014792:Visual Acuity
D017245:Foscarnet; D015774:Ganciclovir