Clinicians frequently view cytomegalovirus (CMV) disease as occurring in the eyes. This is probably due to the fact that CMV retinitis occurred in up to 40% of patients with advanced AIDS before the introduction of Highly Active Antiretroviral Therapy (HAART); in the era of HAART, the incidence has decreased more than 50%.1

Without treatment, CMV lesions enlarge and develop necrosis and edema of all the layers of the retina, eventually progressing to atrophic scar tissue. Affected tissue is unable to regenerate, and vision is permanently impaired.

The goal of treatment is to prevent further necrosis and loss of vision. Some improvement may be seen on an effective regimen of HAART alone, and it is considered safe to stop maintenance anti-CMV therapy following immune recovery when the CD4 count is stable and is greater than 100 mm-150 mm for 3 months.1,2 This decision should be made only after considering the extent of immune recovery and the degree of vision loss.3 However, there are reports that immune recovery may lead to negative ophthalmic complications in some cases, including uveitis, vitritis, macular and disc edema, and cataract.4 The etiology of this phenomena is not yet clearly understood.

The most common symptom suggesting CMV retinitis is altered vision resulting from floaters, flashing lights, or "cotton spots" depending on the anatomic location of retinal damage. The Amsler Grid is a quick and effective screening tool that can be used easily in the clinical setting; it may also be distributed for self-monitoring. There is a positive result when there is a disruption of the grid lines or an appearance of "cotton spots" within the field of vision on the grid. In the absence of an Amsler Grid, a newspaper can be placed on the floor. There is a positive result when there is a report of missing print or "cotton spots" obscuring the print rather than an inability to read the material. On examination, retinal lesions with exudate and hemorrhages are diagnostic of CMV infection.

While the development of ocular disease poses a serious threat to people with severe immunosuppression, CMV should also be considered as a possible etiology in other AIDS-related illnesses involving the gastrointestinal (GI),2 pulmonary, and central nervous systems (CNS)5 including: colitis, pneumonitis, encephalitis, cerebral mass lesions, polyradiculomyelitis, or transverse myelitis. Although seen much less frequently than retinitis, these infections can be debilitating and life threatening.

GI involvement is most frequently seen in the colon or esophagus and results in mucosal ulcers. Biopsy results positive for CMV inclusions are diagnostic.

Pulmonary disease is seen only rarely, and is more common among persons with immunosuppression resulting from transplants than among AIDS patients. CMV is often cultured from respiratory secretions of immunocompromised persons but is not necessarily the causative agent in respiratory disease. Further investigation, including a lung biopsy, is needed before a definitive diagnosis can be made. Persons with Central Nervous System involvement usually present with fever, lethargy, cranial nerve abnormalities, ataxia, and/or confusion, and progress to a state of being obtunded with flaccid paraplegia without therapy. Results of a lumbar puncture usually show a neutrophilic pleocytosis and CVM DNA or antigen.5

Regardless of the site of infection, the CD4 count has been identified as the best predictor of a person's ability to initiate an effective immune response to CMV, even more so than the HIV viral load. CD4 counts less than 50 have been associated with a greater likelihood of infection.4

The current treatments have not changed dramatically in the past five years and can be found in Table 1. These are based on recommendations from the International AIDS Society6 and are adapted from Medical Management of HIV Infection.3

Possible side effects with CMV treatment include the following:

"     Ganciclovir: neutropenia, thrombocytopenia

"     Foscarnet: renal failure, electrolyte imbalance

"     Cidofovir: renal failure

"     Fomivirsen: lack of systemic protection

"     Valganciclovir: granulocytopenia or neutropenia, anemia, and thrombocytopenia. Also, Valganciclovir has been known to cause birth defects. Effective contraception should be used during dosing and for at least 90 days following treatment with Valganciclovir. For women this means using barrier protection (condoms) and one additional form of contraception (birth control pills, intrauterine device). For men this means using barrier protection (condoms).

Intravenous gancyclovir and foscarnet, or a combination of both medications, are used for treatment in cases involving the GI, pulmonary, or CNS system. Side effects are similar to those mentioned above.

Valganciclovir (Valcyte¨, Roche Pharmaceuticals), a prodrug of ganciclovir, is an oral agent that has been developed for treatment of CMV retinitis in people with AIDS. An oral dose of 900 mg of valganciclovir is comparable to a dose of 5 mg/kg of IV ganciclovir (Cytovene¨, Roche). Studies have demonstrated that this recently approved agent has produced equally effective results in the treatment groups using these medications.6 Similar side effects have been reported including neutropenia, thrombocytopenia, GI distress (nausea, vomiting, diarrhea), fever, headache, insomnia, peripheral neuropathy, and retinal detachment.

Prevention of CMV by early diagnosis of HIV, effective antiretroviral therapy, and regular screening is the best way to avoid complications of this and other opportunistic infections.

Judy K. Shaw is an Adult Nurse Practitioner at the Albany VA Hospital, Albany NY, in the Section of Infectious Disease and a Doctoral Candidate at New York University.  She is a former Nicholas A. Rango HIV Clinical Scholar, and has published and presented talks on HIV-related topics locally and nationally. She is the founding President of the NYS Capital District Chapter of the Association of Nurses in AIDS Care and a member of the HIV/AIDS National Certification Board of Directors.

References

1.   Whitcup S. Cytomegalovirus retinitis in the era of highly active retroviral therapy. JAMA. 2000;282(5):.

2.   Pollok R. Viruses causing diarrhea in AIDS. Novartis Foundation Symposium. 2001;238:.

3.   Bartlett J, Gallant J. Medical Management of HIV Infection (Corrections Edition). Baltimore, Md: Johns Hopkins University Press; 2000.

4.   Whitley, et al. Recommendation for CMV treatment. Archives of Internal Medicine. 1998;158:957.

5.   Maschkle M, Kastrup O, Diener H. CNS manifestations of cytomegalovirus infection: diagnosis and treatment. CNS Drugs. 2001;16(5):.

6.   Curran M, Noble S. Valganciclovir. Drugs. 2001;61(8):.