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reported in children with AIDS for reasons that have not been fully determined.
Infection of the retina developed in patients with high HIV loads, nearly absent
CD4 + lymphocytes, and importantly, periods of prolonged HCMV replication and
presumably viremia. The disease was best characterized by an exuberant inflammation
of the retina associated with infection of the vessels entering the retina from its
anterior surface (Pepose et al. 1987; Glasgow and Weisberger 1994; Rao et al.
1998). Infection could be seen in the perivascular glial cells, neuronal cells, and
pigmented retinal epithelium and associated with the loss of vascular integrity
(Pepose et al. 1987; Glasgow and Weisberger 1994; Rao et al. 1998). Intense
inflammation was associated with loss of retinal structure and in some cases,
edema, detachment of the retina and loss of vision. Antiviral therapy, both local and
systemic, that effectively inhibited virus replication also halted disease progression
and led to resolution of the acute symptoms of the disease. Yet virus remained in
the retina and disease recurrence and reinfection of other areas of the retina or the
other eye were considered as part of the natural history of this infection. Prior
to HAART, anti-HCMV drugs were continued for the life of the patient. Once
HAART protocols that limited HIV replication and reversed the immunodeficiency
associated with the late stages of AIDS were in widespread use, the incidence of
HCMV retinitis fell dramatically, and today it is seen in patients who have failed
HAART protocols either because of: (a) HIV drug resistance, (b) noncompliance,
or (c) a first diagnosis in late stage AIDS (Whitcup et al. 1999; Torriani et al. 2000).
In resource-limited regions of the world, CMV retinitis remains an important
opportunistic infection in AIDS patients.
An interesting syndrome was reported by investigators who had successfully
treated AIDS patients with HAART. In these patients, anti-HCMV antiviral therapy
was discontinued once there was evidence of HIV suppression and immune recon-
stitution. These investigators noted that several patients with retinitis with improving
immune function developed a recurrence of their retinitis that was associated with
prominent findings of uveitis and less convincing findings of progressive HCMV
retinitis; they coined the term immune recovery uveitis (IUR) for this syndrome
(Karavellas et al. 1998; Holland 1999). It was suggested that following reconstitution
of HCMV CD8 + responses in patients treated with HAART, clearance of the
HCMV-infected cells in the retina by the reconstituted cytotoxic response could
lead to an exacerbation of local disease by immunopathogenic mechanisms. The
immunopathogenesis of this syndrome remains unclear at this time; however,
several risk factors have been identified for development of IRU. These include
response to HAART with drop in viral load, greater than 25%-30% surface area of
retinal involvement at time of active retinitis, and treatment with the potent antiviral
cidofovir (Karavellas et al. 2001; Kempen et al. 2006). More recent studies of one
cohort of patients revealed that aqueous humor from the involved eye contained
high levels of IL-12, moderate levels of IL-6, interferon gamma, but no viral DNA
(Schrier et al. 2006). These latter findings together with early findings demonstrating
the presence of CD8 + lymphocytes in the involved eyes and clinical response to
intraocular corticosteroids suggested that IUR was an immunopathogenic response
to HCMV infection.
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