Association of Ganciclovir-resistant Cytomegalovirus (CMV) With Adverse Ocular Outcomes in Patients with AIDS and CMV Retinitis

Abstract

Abstract: : Purpose: To determine whether phenotypic and genotypic resistance of cytomegalovirus (CMV) to ganciclovir is associated with retinal measures of extent of disease and with vision loss. Methods: One hundred ninety-seven patients with AIDS and CMV retinitis were enrolled in a prospective, multicenter cohort study and subsequently treated with ganciclovir. Ophthalmologic examination, fundus photography, and visual acuity assessment were performed monthly. Fundus photographs were evaluated in a masked fashion by a central reading center for retinitis progression and retinal area affected. Visual acuity was assessed with logarithmic charts. Blood and urine specimens were cultured at enrollment, at 1 and 3 months after enrollment, and every 3 months thereafter. Positive cultures were tested for phenotypic and genotypic resistance to ganciclovir. Phenotypic resistance was defined as an IC₅₀≷6.0 for blood or an IC₅₀≷8.0 for urine isolates. Genotypic resistance was defined as the presence of a UL97 mutation known to confer resistance to ganciclovir. Time-dependent analyses using 3-month intervals were performed with generalized estimating equations regression methods to evaluate the association of resistance with retinal measures of the extent of disease and with vision loss, while adjusting for CMV treatment and highly active antiretroviral therapy (HAART). Results: Median follow-up time was 9.2 months. Phenotypic resistance was detected in 19 patients, and genotypic resistance in 18. Depending on the type of resistance and specimen source, resistance was associated with an odds ratio of 4.17 to 5.61 (p-values all ≤0.0002) for retinitis progression. Resistance also was associated with a greater increase in the percent of retina affected (median 1.10% versus 0.05 to 0.10% per 3 months, p=0.012 to 0.098). The data were suggestive of a greater loss of visual acuity in the worse eye for patients in the lower end of the population distribution (p=0.009 to 0.096). Conclusion: The risk of adverse ocular outcomes in people with CMV retinitis is increased when resistance to ganciclovir is detected in either the blood or urine.

Keywords: 311 AIDS/HIV • 353 clinical (human) or epidemiologic studies: outcomes/complications • 382 cytomegalovirus