54 research outputs found
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Development of cytomegalovirus (CMV) immune recovery uveitis is associated with Th17 cell depletion and poor systemic CMV-specific T cell responses.
Backgroundthe immune reconstitution inflammatory syndromes (IRIS) are a spectrum of inflammatory conditions associated with opportunistic infections and occurring in approximately16% of human immunodeficiency type 1 (HIV-1)-infected patients given antiretroviral therapy. It has been proposed that these conditions are linked by a dysregulated immune system that is prone to exaggerated responses. However, immunologic studies have been limited by the availability of longitudinal samples from patients with IRIS and appropriate matched control subjects. Cytomegalovirus (CMV) immune recovery uveitis (IRU) is an IRIS occurring in up to 38% of patients with CMV retinitis. Although the pathologic immune responses occur in the eye, immune dysregulation that allows for development of pathologic responses is presumably caused by faulty systemic immune cell reconstitution.Methodswe examined CMV-specific T cell responses, regulatory T (T(reg)) cell function and polyclonal T cell responses, including IL-17 production, in 25 patients with CMV IRU and 49 immunorestored control subjects with CMV retinitis who did not develop IRU.Resultspatients with CMV IRU had poor CMV-specific CD4(+) T cell responses, as compared with control subjects, whereas CD8(+) T cell responses were comparable. Patients with CMV IRU were characterized by smaller numbers of circulating Th17 cells. Deficiency in anti-CMV responses was not associated with differences in T(reg) cell function.Conclusionsthe T(reg) cell compartment is intact in patients with CMV IRU, and these patients do not develop exaggerated systemic CMV-specific or polyclonal immune responses. Cases are instead characterized by more profound depletion of Th17 cells and poor antiviral immune responses. CMV IRU may be most likely to develop in persons experiencing the greatest degree of immune dysfunction before initiating highly active antiretroviral therapy
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Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial: 5. Clinical Features of Cytomegalovirus Retinitis at Diagnosis
To examine associations of systemic and ocular characteristics with severity of cytomegalovirus (CMV) retinitis at time of diagnosis and to compare ocular characteristics of eyes with and without CMV retinitis.
Eleven clinical centers, a data coordinating center, and a fundus photograph reading center participated in a randomized, controlled, multicenter clinical trial comparing foscarnet and ganciclovir as primary therapy for previously untreated CMV retinitis in 240 patients with AIDS.
The systemic characteristics marginally associated with the percentage of retina affected by CMV in a patient's worse eye at diagnosis were chronic fever, weight loss, and number of HIV-related illnesses. A positive CMV blood culture at diagnosis was similarly associated with bilateral disease. Laboratory measures of disease did not correlate well with measures of CMV retinitis severity. Many eyes with CMV retinitis had no or minimal lesion hemorrhage, but most had signs of inflammation. Patients often reported visual symptoms for involved eyes. The worse eyes (the eye with lesions covering the most retinal area) of patients with bilateral disease had greater retinal involvement, more lesions, and fewer degrees of visual field than did involved eyes of patients with unilateral disease. Visual symptoms, inflammation, indolent retinitis, and hemorrhagic lesions were associated with a greater percentage of retina affected by CMV.
The findings support viremia as a mechanism of spread for untreated disease. Visual symptoms and signs of ocular inflammation were indicators both of the presence of CMV retinitis and of greater extent of retinal area covered by CMV retinitis lesions
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Rhegmatogenous Retinal Detachment in Patients With Cytomegalovirus Retinitis: The Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial
To determine the incidence and risk factors for rhegmatogenous retinal detachment in a population of patients with newly diagnosed cytomegalovirus retinitis.
Analysis of selected baseline and time-dependent data on patients enrolled in a multicenter, prospective, randomized, controlled clinical trial of therapy with foscarnet vs ganciclovir.
In 316 eyes with cytomegalovirus retinitis at baseline, the risk of rhegmatogenous retinal detachment in an eye involved by cytomegalovirus retinitis was 18.9% at 6 months (95% confidence interval [CI], 14.0% to 23.8%) and 37.9% at 1 year (95% CI, 30.5% to 45.3%). Retinal detachment was not associated with the type of anticytomegalovirus therapy (intravenous foscarnet or ganciclovir) to which the patient was assigned. Extent of retinal involvement by cytomegalovirus retinitis, higher patient age, and lower CD4+ T-cell counts were associated with an increased risk of retinal detachment; myopia was not.
Retinal detachment in patients with cytomegalovirus retinitis is unrelated to the type of intravenous therapy used or to refractive error. The median time to retinal detachment in an involved eye with cytomegalovirus retinitis and free of retinal detachment at baseline was 18.2 months. Strategies to reduce the extent of retinitis and possibly the number of reactivations may reduce the incidence of retinal detachment
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