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Non-cytomegalovirus ocular opportunistic infections in patients with acquired immunodeficiency syndrome.

ABSTRACT: To report the incidence and clinical outcomes of non-cytomegalovirus (non-CMV) ocular opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) in the era of highly active antiretroviral therapy.Multicenter, prospective, observational study of patients with AIDS.Medical history, ophthalmologic examination, and laboratory tests were performed at enrollment and every 6 months subsequently. Once an ocular opportunistic infection was diagnosed, patients were seen every 3 months for outcomes.At enrollment, 37 non-CMV ocular opportunistic infections were diagnosed: 16 patients, herpetic retinitis; 11 patients, toxoplasmic retinitis; and 10 patients, choroiditis. During the follow-up period, the estimated incidences (and 95% confidence intervals [CI]) of these were: herpetic retinitis, 0.007/100 person-years (PY) (95% CI 0.0004, 0.039); toxoplasmic retinitis, 0.007/100 PY (95% CI 0.004, 0.039); and choroiditis, 0.014/ 100 PY (95% CI 0.0025, 0.050). The mortality rates appeared higher among those patients with newly diagnosed or incident herpetic retinitis and choroiditis (rates = 21.7 deaths/100 PY [P = .02] and 12.8 deaths/100 PY [P = .04]), respectively, than those for patients with AIDS without an ocular opportunistic infection (4.1 deaths/100 PY); toxoplasmic retinitis did not appear to be associated with greater mortality (6.4/100 PY, P = .47). Eyes with newly diagnosed herpetic retinitis appeared to have a poor visual prognosis, with high rates of visual impairment (37.9/100 PY) and blindness (17.5/100 PY), whereas those outcomes in eyes with choroiditis appeared to be lower (2.3/100 PY and 0/100 PY, respectively).Although uncommon, non-CMV ocular opportunistic infections may be associated with high rates of visual loss and/or mortality.

SUBMITTER: Gangaputra S

PROVIDER: S-EPMC4164649 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Non-cytomegalovirus ocular opportunistic infections in patients with acquired immunodeficiency syndrome.

Gangaputra Sapna S Drye Lea L Vaidya Vijay V Thorne Jennifer E JE Jabs Douglas A DA Lyon Alice T AT

American journal of ophthalmology 20121012 2

<h4>Purpose</h4>To report the incidence and clinical outcomes of non-cytomegalovirus (non-CMV) ocular opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) in the era of highly active antiretroviral therapy.<h4>Design</h4>Multicenter, prospective, observational study of patients with AIDS.<h4>Methods</h4>Medical history, ophthalmologic examination, and laboratory tests were performed at enrollment and every 6 months subsequently. Once an ocular opportunistic infecti ...[more]

PMID: 23068916

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Project description:To evaluate the risk of cataract in the setting of AIDS.Prospective cohort study.Subjects with AIDS free of ocular opportunistic infections throughout catamnesis.From 1998 through 2008, subjects 13 years of age or older were enrolled. Demographic characteristics and clinical characteristics were documented at enrollment and semiannually.Cataract was defined as high-grade lens opacity observed by biomicroscopy judged to be the cause of a best-corrected visual acuity worse than 20/40. Eyes that underwent cataract surgery during follow-up were considered to have developed cataract before the first visit when pseudophakia or aphakia was observed.Among 1606 participants (3212 eyes) at enrollment, 1.9% (95% confidence interval [CI]: 1.3%-2.7%) were observed to have cataract or prior cataract surgery. Among the 2812 eyes initially free of cataract and followed longitudinally (median follow-up, 4.6 years), the incidence of cataract was 0.37%/eye-year (95% CI: 0.26%-0.53%). In addition to age, significant cataract risk factors included prior cataract in the contralateral eye (adjusted hazard ratio [aHR], 21.6; 95% CI: 10.4-44.8), anterior segment inflammation (aHR, 4.40; 95% CI: 1.64-11.9), prior retinal detachment (aHR, 4.94; 95% CI: 2.21-11.0), and vitreous inflammation (aHR, 7.12; 95% CI: 2.02-25.0), each studied as a time-updated characteristic. Detectable human immunodeficiency virus RNA in peripheral blood was associated with lower risk of cataract at enrollment (adjusted odds ratio, 0.32; 95% CI: 0.12-0.80) but not of incident cataract (aHR, 1.58; 95% CI: 0.90-2.76). After adjustment for other factors, neither the then-current absolute CD4+ T-cell count nor antiretroviral therapy status showed consistent association with cataract risk, nor did an additive diagnosis of other comorbidities. Compared with the available population-based studies that used similar definitions of cataract, the age-specific prevalence of cataract in our cohort was higher than in 1 of 2 such studies, and the age-specific incidence of cataract surgery was higher.Our results suggest cataract may occur earlier among patients with AIDS free of ocular opportunistic infections than in the general population. Cataract risk was associated most strongly with age and with other ocular morbidity in this population. With improved survival, the burden of cataract likely will increase for persons with the human immunodeficiency virus or AIDS.

Project description:Human cytomegalovirus (HCMV) is an opportunistic human herpesvirus that causes a sight-threatening retinitis in immunosuppressed patients, especially those with AIDS. Using an established model of experimental murine cytomegalovirus (MCMV) retinitis in mice with retrovirus-induced immunodeficiency (MAIDS), we have been attempting to define with greater clarity the immunologic mechanisms that contribute to the progression of AIDS-related HCMV retinitis in the unique immunosuppressive setting of HIV infection. Toward this end, we provide herein a comprehensive assessment of immune response gene expression during the onset and development of MAIDS-related MCMV retinitis employing NanoString nCounter. In so doing, we analyzed and compared the intraocular expressions of 561 immune response genes within MCMV-infected eyes of groups of healthy mice, MCMV-infected mice with MAIDS of 4 weeks' (MAIDS-4) duration, and MCMV-infected eyes of mice with MAIDS of 10 weeks' (MAIDS-10) duration. These animal groups show a progression of retinal disease from absolute resistance to retinitis development in healthy mice to the development of classic full-thickness retinal necrosis in MAIDS-10 mice but through an intermediate stage of retinal disease development in MAIDS-4 mice. Our findings showed that increased susceptibility to MCMV retinitis during the progression of MAIDS is associated with robust upregulation or downregulation of a surprisingly large number of immune response genes that operate within several immune response pathways often unique to each animal group. Analysis of 14 additional immune response genes associated with programmed cell death pathways suggested involvement of necroptosis and pyroptosis during MAIDS-related MCMV retinitis pathogenesis. Use of the NanoString nCounter technology provided new and unexpected information on the immunopathogenesis of retinitis within MCMV-infected eyes of mice with retrovirus-induced immunosuppression. Our findings may provide new insights into the immunologic events that operate during the pathogenesis of AIDS-related HCMV retinitis.

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Non-cytomegalovirus ocular opportunistic infections in patients with acquired immunodeficiency syndrome.

Publications

Non-cytomegalovirus ocular opportunistic infections in patients with acquired immunodeficiency syndrome.

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