Cytomegalovirus retinitis in a patient with late diagnosis of HIV disease
Cytomegalovirus retinitis in a patient with late diagnosis of HIV disease |
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Key words: cytomegalovirus, retinitis, HIV disease
Introduction
The introduction of HAART has coincided with dramatic reduction in opportunistic infections in HIV positive individuals. Recent increase in the number of HIV cases coupled with late diagnosis pose a serious challenge to clinicians. We illustrate a patient with late diagnosis of HIV with multiple opportunistic infections.
Case Report
Mrs AO, a 34 years old lady originally from Cameroon but has been living in UK for the last 4 years was admitted through the Accident and Emergency department with history of fever, shortness of breath, loss of weight and generally feeling unwell. Chest examination showed generalised wheeze, and exercise oximetry showed oxygen saturation of 98% at rest which dropped significantly to 70% with exercise and her Chest X-ray was highly suspicious of pneumocystis pneumonia. She was soon counselled for an HIV test and a bronchoscopy was urgently performed which confirmed the presence of Pneumocystis jiroveci oocysts. The HIV test was reported to be positive and she was started on intravenous septrin at a dose of 120mg/Kg body wt. Whilst in hospital, her HIV viral load was found to be 260,000 copies/ml and her initial CD4 count was profoundly low at 5 cells (1%). Also her toxoplasma serology was suspicious at a dye test titre of 4000 iu. Three weeks later, she was seen in the outpatient department in which she showed very good recovery from her chest symptoms and she was shifted to septrin maintenance dose. Also, we started her on Combivir and escalating dose of Nevirapine. In the follow up appointment two weeks later, a full blood count confirmed a significant drop in her haemoglobin so zidovudine was changed to enteric coated Didanosine 400mg daily. She mentioned that she was tolerating her antiretrovirals very well, yet she was experiencing the occasional blurring of vision. Ophthalmoscopic examination of her left eye showed greyish white fluffy patches in the superio-lateral aspect of the retina which was mainly peripheral and reaching zone 1 with minimal haemorrhages. The right eye was normal. Given her immune compromised status, a provisional diagnosis of Cytomegalovirus (CMV) retinitis was made. CMV viraemia was noted at a viral load of 6,500 copies. She was re-admitted to the hospital and through a central line, ganciclovir at a dose of 5mg/Kg-body weight was given twice daily as induction. Shortly after, significant improvement in her visual field was noted, and the ophthalmologists confirmed that there was no evidence of Toxoplasma choroidoretinitis. Following a two week stay in hospital, she requested to go home and we changed her medication to oral Valganciclovir 900mg twice daily for a further week then maintained on 900mg once daily thereafter. A fortnight later, she was reviewed in the outpatients and her ophthalmoscopic examination was satisfactory. Also, her HIV viral load has dropped four logs and her CD4 cell count has risen considerably on HAART while she is still on secondary prophylactics for CMV, PCP and
Toxoplasma.
Discussion
Cytomegalovirus (CMV) has been a major cause of morbidity and mortality in patients with AIDS.(1) Epidemiological studies indicated that through 1992 nearly half of HIV-infected patients eventually developed CMV end-organ disease including chorioretinitis, esophagitis, colitis, pneumonia, and central nervous system disease.(2) With the advent of highly active antiretroviral treatment (HAART) there has been a dramatic decline in the occurrence of CMV disease in AIDS patients to approximately 5-10% of previous estimates. A diagnosis of CMV disease can be based on clinical evaluation (eg, CMV retinitis) but often requires tissue biopsy with
histologic evidence of viral inclusions and inflammation (eg, CMV colitis).(3) A positive CMV culture of blood, urine, or even biopsy tissue may only reflect active infection rather than true end-organ disease. Detection of CMV antigens or nucleic acids in tissue specimens are alternative, but less conclusive, methods for making a diagnosis of CMV disease. In the patients who have AIDS, progressive loss of immune function, and, in particular, loss of cell-mediated immunity, encourages active CMV replication. Asymptomatic excretion of CMV in urine can be detected in approximately 50% of HIV-infected individuals with a CD4 lymphocyte count below 100 cells/mm3. (4) Transient episodes of CMV viraemia can also occur.(5) Although the clinical significance of viraemia is uncertain, such episodes probably result in dissemination of CMV to other organs (eg, the retina), thereby setting the stage for subsequent end-organ disease. At autopsy, greater than 90% of patients with AIDS have evidence of disseminated CMV infection. (6) HAART leads to at least a partial return of CMV immune responses in most patients and substantial decreases in CMV titers in blood. (7) Thus, in year 2003, CMV retinitis is usually seen in those who have not begun or cannot tolerate HAART. CMV retinitis is relatively rare in patients who fail HAART and have rising HIV viral loads. There appears to be a prolonged lag time between failure of HAART and impairment of CMV immune responses to an extent that allows CMV retinitis to develop. Apparently, a critical level of CMV replication is required for CMV disease to develop, and as long as the viral load can be kept below this critical level, there is protection against retinitis and other end-organ manifestations. Ophthalmologic examination of patients with CMV retinitis typically reveals large creamy to yellowish-white granular areas with perivascular exudates and hemorrhages. These lesions may occur at either the periphery or center of the fundus. If left untreated, lesions generally progress within 2 to 3 weeks and can result in blindness. Retinitis often begins unilaterally, but progression to bilateral disease is common. Systemic CMV disease involving other viscera may also be present. CMV retinitis accounts for at least 90% of HIV-related infectious retinopathies.(8) Differentiating suspected CMV retinitis from cotton wool spots is essential. Cotton wool spots appear as small, fluffy, white lesions with indistinct margins and are not associated with exudates or hemorrhages. These lesions do not progress and often undergo spontaneous regression. Toxoplasmosis is the second most common opportunistic infection of the eye, but it is not associated with hemorrhage and typically occurs in patients with cerebral toxoplasmosis. Syphilis, herpes simplex virus, varicella-zoster virus, and tuberculosis are other infections that may rarely involve the retina. Patients with confirmed CMV chorioretinitis should begin treatment promptly. A variety of agents have demonstrated efficacy in delaying time to progression of retinitis. The choice of initial treatment should be based on several factors, including the patient's clinical status (especially underlying myelosuppression or renal impairment), location of lesion (sight threatening or not), concomitant medication (with potentially overlapping toxicity), and patient preference (especially regarding placement of an indwelling intravenous catheter). Ganciclovir (Cytovene, DHPG) is an acyclic nucleoside analogue of guanine that is a potent inhibitor of CMV replication in vitro.(9) For induction therapy, ganciclovir is given at an intravenous dose of 5 mg/kg twice daily for 2 to 3 weeks or until stabilization of retinitis. Maintenance therapy with ganciclovir (5 mg/kg) is administered once daily. Ganciclovir undergoes renal elimination, so dose reduction in patients with renal insufficiency is required. However, intravenous ganciclovir has been supplemented by valganciclovir (Valcyte), the more convenient oral prodrug of ganciclovir. Valganciclovir at a dose of 900 mg (two 450-mg tablets) orally results in ganciclovir blood levels similar to those obtained with a dose of 5 mg/kg intravenous ganciclovir, and has been shown to be similar in efficacy to intravenous ganciclovir in treating HIV-associated CMV retinitis.(10) Other agents used in the treatment of CMV retinitis include Foscarnet, Cidofovir and Intravitreal ganciclovir applications have also been described.
After 3 months of treatment with intravenous ganciclovir, approximately 8% of patients excrete ganciclovir-resistant strains of CMV in their urine.(11) Development of resistance is associated with a more rapid progression of retinitis, and such individuals can often be identified clinically by a failure to respond to reinduction ganciclovir therapy, when Foscarnet or Cidofovir will be possible alternatives.
References
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