Cytomegalovirus

Question 1

What is Cytomegalovirus (CMV)?

Answer 1

A double-stranded DNA virus in the herpesvirus family that can cause disseminated or localized end-organ disease.

Question 2

In which population does CMV end-organ disease primarily occur?

Answer 2

In people with HIV and advanced immunosuppression, typically with CD4+ T lymphocyte counts <50 cells/mm3.

Question 3

What is the most common CMV end-organ disease in patients with AIDS?

Answer 3

CMV retinitis.

Question 4

What percentage of patients with AIDS experienced CMV retinitis before potent ART?

Answer 4

An estimated 30%.

Question 5

How much has the incidence of new cases of CMV end-organ disease declined with ART?

Answer 5

By ≥95%.

Question 6

What is the recurrence rate of CMV retinitis lesions after immune recovery?

Answer 6

0.03/person-year.

Question 7

What is the characteristic appearance of CMV retinitis lesions?

Answer 7

Fluffy, yellow-white retinal lesions with tiny dry-appearing, granular, dot-like ‘satellites’.

Question 8

What are common clinical manifestations of CMV colitis?

Answer 8

• Weight loss
• Fever
• Anorexia
• Abdominal pain
• Diarrhea
• Malaise

Question 9

What symptoms are associated with CMV esophagitis?

Answer 9

• Odynophagia
• Nausea
• Midepigastric discomfort
• Retrosternal discomfort
• Fever

Question 10

Is CMV pneumonitis common in people with HIV?

Answer 10

No, it is uncommon.

Question 11

What are the key features of CMV neurologic disease?

Answer 11

• Dementia
• Ventriculoencephalitis
• Polyradiculomyelopathy

Question 12

How is CMV retinitis diagnosed?

Answer 12

By recognizing characteristic retinal changes during an ophthalmoscopic examination.

Question 13

What is the diagnostic value of PCR for CMV in aqueous or vitreous humor?

Answer 13

It is useful for establishing the diagnosis in unclear cases.

Question 14

What histopathological feature is indicative of CMV colitis?

Answer 14

Mucosal ulcerations with characteristic intranuclear and intracytoplasmic inclusions.

Question 15

What is the primary preventive measure for CMV end-organ disease?

Answer 15

Maintaining CD4 count >100 cells/mm3 with ART.

Question 16

What is the recommendation for patients with low CD4 counts regarding ocular health?

Answer 16

Regular assessment of visual acuity and referral to ophthalmology for changes.

Question 17

What is the first-line therapy for treating CMV retinitis?

Answer 17

• Oral valganciclovir
• Intravenous ganciclovir
• IV ganciclovir induction followed by oral valganciclovir maintenance

Question 18

What are the potential toxicities of IV foscarnet and IV cidofovir?

Answer 18

• Nephrotoxicity

Question 19

What is the recommended approach for lesions immediately threatening sight?

Answer 19

Supplement systemic therapy with intravitreous injections of ganciclovir or foscarnet.

Question 20

What is the significance of serum antibodies to CMV?

Answer 20

A negative IgG antibody level indicates that CMV is unlikely to be the cause of the disease process.

Question 21

Fill in the blank: CMV is shed in ______, cervical secretions, and saliva.

Answer 21

semen

Question 22

True or False: A positive PCR assay for CMV in blood is sufficient to diagnose CMV end-organ disease.

Answer 22

False.

Question 23

What is the primary treatment for immediate sight-threatening lesions in CMV retinitis?

Answer 23

Intravitreal injections of ganciclovir or foscarnet

Question 24

How often are intravitreal injections continued until lesion inactivity is achieved?

Answer 24

Weekly

Question 25

What is the rationale for supplementing systemic therapy with intravitreal injections?

Answer 25

Based on pharmacokinetic considerations

Question 26

What complications can arise from intravitreal injections?

Answer 26

* Bacterial or fungal infections * Hemorrhage * Retinal detachment

Question 27

What is the recommended treatment for patients without sight-threatening lesions?

Answer 27

Oral valganciclovir alone

Question 28

What is the duration of systemic anti-CMV therapy recommended for patients until ART induces immune recovery?

Answer 28

3 to 6 months

Question 29

What ocular complications are related to lesion size in CMV retinitis?

Answer 29

* Immune recovery uveitis (IRU) * Retinal detachment

Question 30

What is the therapy of choice for patients with colitis or esophagitis?

Answer 30

IV ganciclovir

Question 31

What alternative can be used if ganciclovir-related toxicity is treatment-limiting?

Answer 31

Foscarnet

Question 32

What is the concern regarding IRIS after ART initiation?

Answer 32

Substantial increase in immune reconstitution uveitis (IRU)

Question 33

When should ART be initiated after starting anti-CMV therapy?

Answer 33

No later than 1 to 2 weeks

Question 34

What is the purpose of indirect ophthalmoscopy in managing CMV retinitis?

Answer 34

* Evaluate efficacy of treatment * Identify second eye involvement * Detect complications like IRU

Question 35

What are the adverse effects of ganciclovir/valganciclovir?

Answer 35

* Anemia * Neutropenia * Thrombocytopenia * Nausea * Diarrhea * Renal dysfunction

Question 36

What should be monitored in patients receiving foscarnet?

Answer 36

* Serum electrolytes * Renal function * Complete blood counts

Question 37

What adverse effects are associated with cidofovir?

Answer 37

* Nephrotoxicity * Neutropenia * Uveitis * Hypotony

Question 38

What is immune recovery uveitis (IRU)?

Answer 38

An ocular form of IRIS characterized by inflammation in the anterior chamber or vitreous body

Question 39

What is the estimated incidence of IRU after immune recovery?

Answer 39

0.02/person-year

Question 40

What is the recommended treatment for IRU?

Answer 40

Corticosteroid therapy

Question 41

When can maintenance therapy for CMV retinitis be safely discontinued?

Answer 41

After lesions have been inactive for 3 to 6 months with sustained increases in CD4 cell counts

Question 42

What monitoring is required after discontinuing anti-CMV maintenance therapy?

Answer 42

Ophthalmologic monitoring every 3 months

Question 43

What is the risk of reactivation of CMV retinitis after stopping maintenance therapy?

Answer 43

3%

Question 44

What is a potential cause of therapy failure in CMV retinitis?

Answer 44

Inadequate anti-CMV drug levels in the eye

Question 45

What is the resistance rate for ganciclovir in the pre-ART era?

Answer 45

Approximately 25% per person-year

Question 46

How can ganciclovir resistance be detected?

Answer 46

CMV DNA PCR of blood specimens followed by detection of UL97 mutations

Question 47

What is the role of oral valganciclovir in maintenance therapy?

Answer 47

Easiest and least toxic to administer to an outpatient population

Question 48

What is the recommended frequency for ophthalmologic monitoring after discontinuing anti-CMV maintenance therapy?

Answer 48

At least every 3 months and periodically after immune reconstitution. ## Footnote Monitoring is crucial for early detection of CMV relapse and IRU.

Question 49

At what CD4 cell count should maintenance therapy be reinstituted?

Answer 49

When the CD4 cell count has decreased to <100 cells/mm3. ## Footnote Reactivation of CMV retinitis occurs frequently in patients with CD4 <50 cells/mm3.

Question 50

What are the indications for treatment of CMV infection during pregnancy?

Answer 50

The same as for nonpregnant individuals with HIV. ## Footnote Treatment considerations should include the timing of therapy to limit fetal exposure.

Question 51

What is the preferred therapy for immediate sight-threatening CMV lesions?

Answer 51

Ganciclovir 5 mg/kg IV q12h for 14–21 days, then 5 mg/kg IV daily or valganciclovir 900 mg PO daily. ## Footnote Intravitreous injections may also be used to control infection.

Question 52

What is the teratogenic risk associated with ganciclovir use during pregnancy?

Answer 52

Embryotoxic among rabbits and mice, causing various malformations. ## Footnote Safe use in human pregnancy has been reported in certain populations.

Question 53

What monitoring is recommended if foscarnet is used during pregnancy?

Answer 53

Weekly monitoring of amniotic fluid volumes by ultrasound after 20 weeks of gestation. ## Footnote This is to detect oligohydramnios due to foscarnet's renal toxicity.

Question 54

What should be monitored in the fetus during the third trimester of pregnancy?

Answer 54

Fetal movement counting and periodic ultrasound monitoring. ## Footnote This is to check for hydrops fetalis indicating substantial anemia.

Question 55

What are the risk factors for congenital CMV?

Answer 55

* Mothers with CD4+ <200 cells/mm3 * Mothers with urinary CMV shedding * HIV transmission to infants. ## Footnote Maternal CMV and infant congenital CMV are linked to increased risk of HIV perinatal transmission.

Question 56

What is the recommendation for treating asymptomatic maternal CMV infection during pregnancy?

Answer 56

Treatment is not indicated solely to prevent infant infection. ## Footnote Routine screening for CMV infection in pregnancy is not recommended.

Question 57

What is the classification of the therapy for CMV retinitis based on patient tolerance?

Answer 57

Therapy should be individualized based on tolerance of systemic medications, prior exposure to anti-CMV drugs, and lesion location. ## Footnote Individualized treatment improves outcomes.

Question 58

What is the duration of anti-CMV therapy for CMV esophagitis or colitis?

Answer 58

21–42 days or until signs and symptoms have resolved. ## Footnote Maintenance therapy is usually not necessary but should be considered after relapses.

Question 59

What is the recommended therapy for managing well-documented CMV pneumonitis?

Answer 59

Use of IV ganciclovir or IV foscarnet is reasonable. ## Footnote Treatment experience for CMV pneumonitis in HIV patients is limited.

Question 60

What combination therapy may be used for managing CMV neurological disease?

Answer 60

Ganciclovir IV plus foscarnet IV to stabilize disease. ## Footnote Prompt initiation of treatment is crucial.

Question 61

What is the role of oral valganciclovir in the treatment of CMV neurological disease?

Answer 61

The role has not been established. ## Footnote Further research is needed to determine its effectiveness.

Question 62

What is the optimal duration of therapy for CMV retinitis?

Answer 62

Not established. ## Footnote Treatment should be initiated promptly to prevent complications.