Cytomegalovirus Disease

Prevention of Exposure
(1) HIV-infected persons who belong to risk groups with relatively low rates of seropositivity for cytomegalovirus (CMV) and therefore cannot be presumed to be seropositive, should be tested for antibody to CMV (BIII). These groups include patients who have had neither male homosexual contact nor used injection drugs.

(2) HIV-infected adolescents and adults should be advised that CMV is shed in semen, cervical secretions, and saliva and that latex condoms must always be used during sexual contact to reduce the risk of exposure to CMV and to other sexually transmitted pathogens (AII).

(3) HIV-infected adults and adolescents who are child-care providers or parents of children in child-care facilities should be informed that they are at increased risk of acquiring CMV infection (BI). Similarly, parents and other care-takers of HIV-infected children should be advised of the increased risk to children at these centers (BIII). The risk of acquiring CMV infection can be diminished by good hygienic practices such as hand washing (AII).

(4) HIV-exposed infants and HIV-infected children, adolescents, and adults who are seronegative for CMV and require blood transfusion should be administered only CMV antibody-negative or leukocyte-reduced cellular blood products in non-emergency situations (BIII).

Prevention of Disease
(5) Prophylaxis with oral ganciclovir may be considered for HIV-infected adults and adolescents who are CMV seropositive and who have a CD4+ T-lymphocyte count of <50 cells/uL (CI) (57, 58). Ganciclovir-induced neutropenia, anemia, conflicting reports of efficacy, lack of proven survival benefit, the risk of developing ganciclovir resistant CMV, and cost are among the issues that should be considered in decisions about whether to institute prophylaxis in individual patients. Acyclovir is not effective in preventing CMV disease, and valacyclovir is not recommended because of an unexplained trend toward increased mortality observed in persons who have AIDS and who were administered this drug for CMV prophylaxis. Therefore, neither acyclovir nor valaciclovir should be used for this purpose (EI). The most important method for preventing severe CMV disease is recognition of the early manifestations of the disease. Early recognition of CMV retinitis is most likely when the patient has been educated on this topic. Patients should be made aware of the significance of increased "floaters" in the eye and should be advised to assess their visual acuity regularly by simple techniques such as reading newsprint (BIII). Regular funduscopic examinations performed by a health-care provider or specifically by an ophthalmologist are recommended by some experts for patients with low (e.g., <50 cells/uL) CD4+ T-lymphocyte counts (CIII).

Prevention of Recurrence
(6) CMV disease is not cured with courses of the currently available antiviral agents (i.e., ganciclovir, foscarnet, or cidofovir). Following induction therapy, secondary prophylaxis (chronic maintenance therapy) is recommended for life (AI). Regimens that are effective for chronic suppression include parenteral or oral ganciclovir, parenteral foscarnet, combined parenteral ganciclovir and foscarnet, parenteral cidofovir, and (for retinitis only) ganciclovir administration via intraocular implant (AI) (59-63). The intraocular implant alone does not provide protection to the contralateral eye or to other organ systems. The choice of a chronic maintenance regimen for patients treated for CMV disease should be made in consultation with an expert. For patients with retinitis, this decision should be made in consultation with an ophthalmologist, and should take into consideration the anatomic location of the retinal lesion, vision in the contralateral eye, the immunologic and virologic status of the patient, and response to HAART (BIII).

Discontinuation of Secondary Prophylaxis (chronic maintenance therapy)
(7) Several studies have found results of discontinuing maintenance therapy in patients with CMV retinitis whose CD4+ T-lymphocyte counts have increased to over 100-150 cells/uL and whose HIV plasma RNA has been suppressed in response to HAART. These patients largely continue to remain disease free for > 30-90 weeks, whereas in the pre-HAART era, retinitis typically recurred in 6-8 weeks. Discontinuation of prophylaxis may be considered in patients with a sustained (e.g. >> 3-6 month) increase in CD4 count to > 100-150 cells/uL on HAART (CIII). Such decisions should be made in consultation with an ophthalmologist and should take into account such factors as magnitude and duration of CD4+ T- lymphocyte increase, magnitude and duration of viral load suppression, anatomic location of the retinal lesion, vision in the contralateral eye, and the feasibility of regular ophthalmic monitoring (CII) (64, 65). Prophylaxis should not be discontinued in patients with extraocular CMV disease (DIII).

Restarting Secondary Prophylaxis
(8) There are no data to guide recommendations for reinstitution of secondary prophylaxis. Pending the availability of such data, a reasonable approach would be to restart prophylaxis when the CD4 count has decreased to < 50-100 cells/uL (CIII).

Notes

Pediatric Note
(9) Some experts recommend obtaining a CMV urine culture on all HIV-infected (or exposed) infants at birth or at an early postnatal visit to identify those infants with congenital CMV infection (CIII). In addition, beginning at 1 year of age, CMV antibody testing on an annual basis may be considered for CMV-seronegative (and culture-negative) HIV-infected infants and children who are severely immunosuppressed (Table 7A and 7B) (CIII). Annual testing will allow identification of children who have acquired CMV infection and might benefit from screening for retinitis.

(10) HIV-infected children who are CMV-infected and severely immunosuppressed may benefit from a dilated retinal examination performed by an ophthalmologist every 4-6 months (CIII). In addition, older children should be counseled to be aware of "floaters" in the eye, similar to the recommendation for adults (BIII).

(11) Oral ganciclovir results in reduced CMV shedding in CMV-infected children, and may be considered for primary prophylaxis against CMV disease in severely immunosuppressed (e.g., CD4+ T-lymphocyte count < 50 cells/uL) CMV-infected children (CII).

(12) For children with CMV disease, no data are available to guide decisions concerning discontinuation of secondary prophylaxis (chronic maintenance therapy) when the CD4+ T-lymphocyte count has increased in response to HAART.

Note Regarding Pregnancy
(13) Because of the lack of recommendation for its routine use in nonpregnant adults and the lack of experience with this drug during pregnancy, ganciclovir is not recommended for primary prophylaxis against CMV disease during pregnancy (DIII). Ganciclovir should be discontinued for patients who conceive while being administered primary prophylaxis. Because of the risks to maternal health, prophylaxis against recurrent CMV disease is indicated during pregnancy (AIII). The choice of agents to be used in pregnancy should be individualized after consultation with experts.

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