GUIDELINE WHO CMV

Cytomegalovirus (CMV) is a double-stranded DNA virus in the herpesvirus family that can
cause disseminated or localized end-organ disease in people with HIV with advanced
immunosuppression. Most clinical disease occurs in individuals previously infected with CMV
experiencing reactivation of latent infection.

End-organ disease caused by CMV occurs in patients with HIV and advanced
immunosuppression, typically those with CD4+ T lymphocyte cell (CD4) counts <50
cells/mm3 who are not receiving, adherent to, or responding to antiretroviral therapy (ART).1

MANIFESTASI KLINIS

1. Paling sering adalah retinitis dan biasanya unilateral

Gejalanya adalah : floaters, scotomata, or peripheral visual field defects
Khasnya pada oftalmosokopi: characteristic ophthalmologic appearance is that of fluffy,
yellow-white retinal lesions, with or without intraretinal hemorrhage. The most typical
feature is the lesion border, which has tiny dry-appearing, granular, dot-like “satellites” at the
interface between infected and normal retina. There will be little inflammation of the vitreous
humor unless immune recovery with ART occurs.1 Blood vessels near the lesions may appear
to be sheathed. Occasionally, CMV retinitis lesions, particularly peripheral lesions, may have
only a granular appearance throughout the lesion.

2. Kemudian sering juga menyebabkan gejala GI (akut abdomen) CMV COLITIS

3. Pneumonitis
4. Neurologic

DIAGNOSIS

CMV REITINITIS -> Biasanya dari klinis (ada gangguan maata), kemudian dia tegak dari pcr
cairan aquos nya
CMV COLITIS -> dari endoskopi sama histologi (intranuclear and intracytoplasmic
inclusions on hematoxylin and eosin stains)
CMV ESOFAGITIS -> Culturing CMV, or detection of CMV DNA by PCR, from a biopsy or cells
brushed from the colon or the esophagus is insufficient to establish the diagnosis of CMV
colitis or esophagitis in the absence of histopathologic changes, because a substantial
number of patients with low CD4 cell counts may shed CMV and have positive cultures in the
absence of clinical disease.12
CMV NEUROLOGIC -> clinical syndrome and the presence of CMV in CSF or brain tissue,
most often evaluated with PCR.

TERAPI
Preventing CMV Disease

 CMV end-organ disease is best prevented by using ART to maintain CD4+ count >100 cells/mm3.

Managing CMV Retinitis

 The choice of therapy for CMV retinitis should be individualized, based on tolerance of systemic medications; pri
anti-CMV drugs; and on the location of lesions (AIII).

 Given the evident benefits of systemic therapy in preventing contralateral eye involvement, reducing CMV viscer
improving survival, treatment should include systemic therapy whenever feasible.
Initial Therapy Followed by Chronic Maintenance Therapy—For Immediate Sight-Threatening Lesions (within 1,5
the fovea)
Preferred Therapy

 Ganciclovir 5 mg/kg IV q12h for 14–21 days, then 5 mg/kg IV daily (AI), or

 Ganciclovir 5 mg/kg IV q12h for 14–21 days, then valganciclovir 900 mg PO daily (AI), or

 Valganciclovir 900 mg PO q12h for 14–21 days, then 900 mg once daily (AI); or
with or without

 Intravitreous injections of ganciclovir (2 mg/injection) or foscarnet (2.4 mg/injection) repeat weekly until lesion i
achieved. This is to provide higher intraocular levels of drug and faster control of the infection until steady-state
ganciclovir concentrations are achieved. (AIII)

o Note: IV ganciclovir can be switched to oral valganciclovir if the patient is clinically improving and there a
about gastrointestinal absorption.
Alternative Therapy

 Intravitreous injections as listed above (AIII); plus one of the following systemic therapies:

o Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h for 14–21 days, then 90–120 mg/kg IV q24h (BI), or

o Cidofovir 5 mg/kg/week IV for 2 weeks, then 5 mg/kg every other week with saline hydration before and a
probenecid 2 g PO 3 hours before the dose followed by 1 g PO 2 hours after the dose, and 1 g PO 8 hours a
 (total of 4 g) (CI). Cidofovir is contraindicated in patients with a serum creatinine >1.5 mg/kL, a calculated
clearance ≤5 mL/min or a urine protein ≥100 mg/kL (equivalent to ≥2+ proteinuria). Given the nephrotoxi
cidofovir, cautious use of cidofovir with tenofovir is advised.

 Note: This regimen should be avoided in patients with sulfa allergy because of cross-hypersensitiv
probenecid.
For Peripheral Lesions

 Valganciclovir 900 mg PO q12h for 14–21 days, then 900 mg once daily (AI) for the first 3–6 months until ART-indu
recovery (AII).
IRU

 Minimizing lesion size by treating all CMV retinitis lesions until there is immune recovery may reduce the inciden

 IRU might develop in the setting of immune reconstitution.

Treatment of IRU

 Periocular or intravitreal corticosteroid or a short course of systemic steroid (BIII).

Stopping Chronic Maintenance Therapy for CMV Retinitis

 CMV treatment for at least 3–6 months, and lesions are inactive, and with CD4+ count >100 cells/mm3

for 3–6 months in response to ART (AII).

 Therapy should be discontinued only after consultation with an ophthalmologist,

taking into account magnitude and duration of CD4 cell count increase, anatomic location of the lesions,

vision in the contralateral eye, and the feasibility of regular ophthalmologic monitoring.

 Routine (i.e., every 3 months) ophthalmologic follow-up is recommended after

stopping chronic maintenance therapy for early detection of relapse or IRU, and then periodically after

sustained immune reconstitution (AIII).

Reinstituting Chronic Maintenance for CMV Retinitis

 CD4 count <100 cells/mm3(AIII).

Managing CMV Esophagitis or Colitis

 Doses are the same as for CMV retinitis.

Preferred Therapy

 Ganciclovir 5 mg/kg IV q12h; may switch to valganciclovir 900 mg PO q12h once the patient

can absorb and tolerate PO therapy (BI).

Alternative Therapy

 Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h (BIII)—for patients with treatment-limiting

toxicities to ganciclovir or with ganciclovir resistance; or

 Oral valganciclovir may be used if symptoms are not severe enough to interfere with oral absorption (BIII);

or
Duration of Anti-CMV Therapy

 21–42 days or until signs and symptoms have resolved (CII).

Note: Maintenance therapy is usually not necessary, but should be considered after relapses (BII).

Managing Well-Documented CMV Pneumonitis

 Doses are the same as for CMV retinitis.

 Treatment experience for CMV pneumonitis in HIV patients is limited. Use of IV ganciclovir or
 IV foscarnet is reasonable (CIII).

 The role of oral valganciclovir has not been established.

 The optimal duration of therapy has not been established.

Managing CMV Neurological Disease

 Doses are the same as for CMV retinitis.

 Treatment should be initiated promptly.

 Combination of ganciclovir IV plus foscarnet IV to stabilize disease and maximize response (CIII).

 Optimal duration of therapy has not been established.

 The role of oral valganciclovir has not been established.

 Optimize ART to achieve viral suppression and immune reconstitution (BIII).