Cytomegalovirus resistance to ganciclovir and clinical outcomes of patients with cytomegalovirus retinitis☆☆☆
Accepted 1 May 2002.
Abstract
Purpose
To evaluate whether cytomegalovirus resistant to ganciclovir, detected in either the blood or urine, correlates with adverse ocular outcomes.
Design
Prospective cohort study.
Methods
Patients with cytomegalovirus and AIDS were enrolled in a study of the occurrence and clinical correlates of resistant cytomegalovirus. Blood and urine cultures for cytomegalovirus were performed at the time of diagnosis of retinitis, 1 and 3 months after the initiation of therapy, and every 3 months thereafter. Patients were seen monthly, at which time fundus photographs were obtained and forwarded to the Fundus Photograph Reading Center for evaluation of retinitis progression (movement of a border of a cytomegalovirus lesion ≥750 μm, or the occurrence of a new lesion ≥ 0.25 disk area in size) and the amount of retinal area affected by cytomegalovirus retinitis. Visual acuity was measured using logarithmic visual acuity charts. Phenotypic resistance to ganciclovir was defined as an IC50 >6.0 μmol/l, and genotypic resistance to ganciclovir was defined as the occurrence of a cytomegalovirus UL97 gene mutation known to confer ganciclovir resistance. Time-dependent analyses were performed and included viral resistance, highly active antiretroviral therapy, and treatment variables as predictors of clinical outcomes.
Results
One hundred ninety-seven patients received ganciclovir therapy. Nineteen patients developed phenotypic resistance to ganciclovir, and 18 developed genotypic resistance. The detection of cytomegalovirus resistant to ganciclovir was associated with a 4.17- to 5.61-fold increase in the odds of retinitis progression (P values all ≤ .0002), depending upon the definition of resistance and the culture sources analyzed. Resistance was associated with a greater increase in retinal area involved by cytomegalovirus by 3-month interval (1.10% vs 0.05% to 0.10%), which was significant for phenotypic resistance and for genotypic resistance in the blood or urine (P = .012 to .021). There was a suggestion that resistance was associated with a greater loss of visual acuity (P = .009 to .096). Highly active antiretroviral therapy was associated with an approximate 50% reduction in the odds of retinitis progression, and the ganciclovir implant was associated with an approximate 60% reduction.
Conclusions
The detection of cytomegalovirus resistant to ganciclovir in either the blood or urine of a patient with cytomegalovirus retinitis is associated with an increased risk of adverse ocular outcomes.
aDepartment of Ophthalmology (D.A.J., J.P.D, J.H.K.), The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
bDepartment of Medicine (D.A.J.), The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
cDepartment of Epidemiology (D.A.J., B.K.M., J.H.K.), The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA
dDepartment of Pathology (M.S.F.), The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
eDepartment of Ophthalmology (L.H.), University of Wisconsin at Madison School of Medicine, Madison, Wisconsin, USA
fDepartment of Ophthalmology (J.L.D.), University of Miami, Miami, Florida, USA
gDepartment of Ophthalmology (D.V.W.), Northwestern University School of Medicine, Chicago, Illinois, USA
Inquiries to Douglas A. Jabs, MD, MBA, 550 North Broadway, Suite 700, Baltimore, MD 21205, USA; fax: (410) 955-0629
☆ This study was supported by Grant EY-10268 (D.A.J.) from the National Eye Institute, National Institutes of Health, Bethesda, Maryland; and by NIH/National Center for Research Resources Grant M01-RR00052 to The Johns Hopkins University School of Medicine.
☆☆ InternetAdvance publication at ajo.com Sept 6, 2002.
ABSTRACT