Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acquired self-limited illness: immunocompetent

1st line – reassurance

Back
ACUTE
|
acquired self-limited illness: immunocompetent
1st line – 

reassurance

Antiviral treatment of cytomegalovirus infection and disease in immunocompetent individuals is not generally recommended because the disease is self-limited.

infection in transplant recipient: no known drug resistance

1st line – intravenous ganciclovir

Back
ACUTE
|
infection in transplant recipient: no known drug resistance
|
with pneumonitis, severe GI disease, or ICU admission
1st line – 

intravenous ganciclovir

There are no guidelines to define severity of disease; a judgement is made by the managing clinician.

Intravenous ganciclovir is the first-line antiviral treatment for severe cytomegalovirus disease, including severe colitis and pneumonitis, and for patients who require admission to the intensive care unit (ICU).

Primary options

ganciclovir: 5 mg/kg intravenously every 12 hours for at least 2-4 weeks and until clinical resolution and CMV is no longer detected in the blood

Consider – immunoglobulins

Back
ACUTE
|
infection in transplant recipient: no known drug resistance
|
with pneumonitis, severe GI disease, or ICU admission
Consider – 

immunoglobulins

Additional treatment recommended for SOME patients in selected patient group

Immunoglobulins (unselected or CMV-hyperimmune globulins) may be used as adjunctive treatment in severe cytomegalovirus (CMV) disease, especially in lung transplant and haematopoietic stem cell transplant patients with CMV pneumonitis, although evidence for a clear benefit is lacking.​[1][51]​​​[62]​​

Primary options

normal immunoglobulin human: consult specialist for guidance on dose

OR

cytomegalovirus immunoglobulin (human): consult specialist for guidance on dose

Consider – step down to oral valganciclovir

Back
ACUTE
|
infection in transplant recipient: no known drug resistance
|
with pneumonitis, severe GI disease, or ICU admission
Consider – 

step down to oral valganciclovir

Additional treatment recommended for SOME patients in selected patient group

Valganciclovir can be used as a rapid step-down approach following initial therapy with intravenous ganciclovir in patients with severe disease.[1]​​

Primary options

valganciclovir: 900 mg orally twice daily for at least 2-4 weeks and until clinical resolution and CMV is no longer detected in the blood

2nd line – intravenous foscarnet

Back
ACUTE
|
infection in transplant recipient: no known drug resistance
|
with pneumonitis, severe GI disease, or ICU admission
2nd line – 

intravenous foscarnet

Foscarnet is a less-preferred choice of therapy because of its associated nephrotoxicity.[1]​​

There are no guidelines to define severity of disease; a judgement is made by the managing clinician.

Primary options

foscarnet: 90 mg/kg intravenously every 12 hours; or 60 mg/kg intravenously every 8 hours for at least 2-4 weeks and until clinical resolution and CMV is no longer detected in blood and tissue specimens

Consider – immunoglobulins

Back
ACUTE
|
infection in transplant recipient: no known drug resistance
|
with pneumonitis, severe GI disease, or ICU admission
Consider – 

immunoglobulins

Additional treatment recommended for SOME patients in selected patient group

Immunoglobulins (unselected or CMV-hyperimmune globulins) may be used as adjunctive treatment in severe cytomegalovirus (CMV) disease, especially in lung transplant and haematopoietic stem cell transplant patients with CMV pneumonitis, although evidence for a clear benefit is lacking.​[1][51]​​​[62]​​

Primary options

normal immunoglobulin human: consult specialist for guidance on dose

OR

cytomegalovirus immunoglobulin (human): consult specialist for guidance on dose

1st line – oral valganciclovir

Back
ACUTE
|
infection in transplant recipient: no known drug resistance
|
without pneumonitis, severe GI disease, or ICU admission
1st line – 

oral valganciclovir

In those patients without severe diarrhoea or problems with absorption, pneumonitis, or need for ICU admission, oral valganciclovir is considered first-line treatment.[52] There are no guidelines to define severity of disease; a judgement is made by the managing clinician.

Primary options

valganciclovir: 900 mg orally twice daily for at least 2-4 weeks and until clinical resolution and CMV is no longer detected in the blood and tissue specimens

2nd line – intravenous ganciclovir

Back
ACUTE
|
infection in transplant recipient: no known drug resistance
|
without pneumonitis, severe GI disease, or ICU admission
2nd line – 

intravenous ganciclovir

Ganciclovir is a less-preferred choice of therapy because of the route of administration.[1]​​

There are no guidelines to define severity of disease; a judgement is made by the managing clinician.

Primary options

ganciclovir: 5 mg/kg intravenously every 12 hours for at least 2-4 weeks and until clinical resolution and CMV is no longer detected in the blood or tissue specimens

3rd line – intravenous foscarnet

Back
ACUTE
|
infection in transplant recipient: no known drug resistance
|
without pneumonitis, severe GI disease, or ICU admission
3rd line – 

intravenous foscarnet

Foscarnet is a less-preferred choice of therapy because of associated nephrotoxicity.[1]​​

There are no guidelines to define severity of disease; a judgement is made by the managing clinician.

Primary options

foscarnet: 90 mg/kg intravenously every 12 hours, or 60 mg/kg intravenously every 8 hours for at least 2-4 weeks and until clinical resolution and CMV is no longer detected in blood and tissue specimens

infection in patient with AIDS: no known drug resistance

1st line – initial antiviral therapy

Back
ACUTE
|
infection in patient with AIDS: no known drug resistance
|
with retinitis (immediate sight-threatening lesions)
1st line – 

initial antiviral therapy

Intravenous ganciclovir or oral valganciclovir, with or without intravitreal ganciclovir or foscarnet, is the preferred initial therapy for patients with immediate sight-threatening lesions. Alternative options include intravitreal ganciclovir or foscarnet in combination with intravenous foscarnet or cidofovir (with probenecid and saline hydration therapy before and after cidofovir therapy).[2]

An ophthalmologist familiar with cytomegalovirus retinitis should ideally be involved in management.[2]

Primary options

ganciclovir: 2 mg intravitreally weekly until lesion inactivity achieved

or

foscarnet: 2.4 mg intravitreally weekly until lesion inactivity achieved

-- AND --

ganciclovir: 5 mg/kg intravenously every 12 hours for 14-21 days

or

valganciclovir: 900 mg orally twice daily for 14-21 days

OR

ganciclovir: 5 mg/kg intravenously every 12 hours for 14-21 days

OR

valganciclovir: 900 mg orally twice daily for 14-21 days

Secondary options

ganciclovir: 2 mg intravitreally weekly until lesion inactivity achieved

or

foscarnet: 2.4 mg intravitreally weekly until lesion inactivity achieved

-- AND --

foscarnet: 60 mg/kg intravenously every 8 hours, or 90 mg/kg intravenously every 12 hours for 14-21 days

OR

ganciclovir: 2 mg intravitreally weekly until lesion inactivity achieved

or

foscarnet: 2.4 mg intravitreally weekly until lesion inactivity achieved

-- AND --

cidofovir: 5 mg/kg intravenously once weekly for 2 weeks

-- AND --

probenecid: 2 g orally 3 hours before cidofovir dose, followed by 1 g given 2 hours and 8 hours after the dose

Plus – antiviral maintenance therapy

Back
ACUTE
|
infection in patient with AIDS: no known drug resistance
|
with retinitis (immediate sight-threatening lesions)
Plus – 

antiviral maintenance therapy

Treatment recommended for ALL patients in selected patient group

Initial therapy (lasting a minimum of 14-21 days, with duration determined by clinical response based on retinal examination) should be followed by chronic maintenance therapy.[2]

Maintenance therapy can be safely discontinued in patients with inactive disease and sustained CD4+ count (>100 cells/microlitre for ≥three to six months); consultation with an ophthalmologist is recommended. Regular eye examinations should be performed every three months in patients who have discontinued maintenance therapy, to ensure early detection of relapse or immune recovery uveitis.[2]

Early relapse is most often caused by the limited intraocular penetration of systemically administered drugs.[54]

If patients relapse while receiving maintenance therapy, reinduction with the same drug followed by reinstitution of maintenance therapy is recommended. Changing to an alternative drug at the time of first relapse should be considered if drug resistance is suspected or if side effects or toxicities interfere with optimal courses of the initial agent.

Primary options

valganciclovir: 900 mg orally once daily

Secondary options

ganciclovir: 5 mg/kg intravenously once daily

OR

foscarnet: 90-120 mg/kg intravenously once daily

OR

cidofovir: 5 mg/kg intravenously every 2 weeks

and

probenecid: 2 g orally 3 hours before cidofovir dose, followed by 1 g given 2 hours and 8 hours after the dose

1st line – antiviral therapy

Back
ACUTE
|
infection in patient with AIDS: no known drug resistance
|
with retinitis (non-sight-threatening lesions)
1st line – 

antiviral therapy

For small peripheral lesions, oral valganciclovir alone may be adequate.[2]

Systemic antiviral therapy is administered for 3-6 months until antiretroviral therapy-induced immune recovery.[2]

Primary options

valganciclovir: 900 mg orally twice daily for 14-21 days, followed by 900 mg once daily

1st line – antiviral therapy

Back
ACUTE
|
infection in patient with AIDS: no known drug resistance
|
with GI disease
1st line – 

antiviral therapy

For gastrointestinal disease (e.g., oesophagitis or colitis), oral valganciclovir, intravenous ganciclovir or foscarnet for 21-42 days (or until signs and symptoms have resolved) is recommended.

Valganciclovir is the first-line treatment if symptoms are not severe enough to interfere with oral absorption.

Maintenance therapy is usually not needed for cytomegalovirus oesophagitis or colitis, but should be considered following relapses.[2][32]

Primary options

valganciclovir: 900 mg orally twice daily

OR

ganciclovir: 5 mg/kg intravenously every 12 hours, may switch to oral valganciclovir once patient can tolerate oral therapy

Secondary options

foscarnet: 60 mg/kg intravenously every 8 hours, or 90 mg/kg intravenously every 12 hours

1st line – antiviral therapy

Back
ACUTE
|
infection in patient with AIDS: no known drug resistance
|
with pneumonitis
1st line – 

antiviral therapy

For pneumonitis, intravenous ganciclovir or foscarnet is used, although few data are available regarding therapy impact outcomes.

The optimal duration of therapy has not been established.[2]

Primary options

ganciclovir: 5 mg/kg intravenously every 12 hours

OR

foscarnet: 60 mg/kg intravenously every 8 hours, or 90 mg/kg intravenously every 12 hours

1st line – antiviral therapy

Back
ACUTE
|
infection in patient with AIDS: no known drug resistance
|
with neurological disease
1st line – 

antiviral therapy

Combination regimen is used to stabilise disease and maximise response.

The optimal duration of therapy has not been established.[2] Maintenance therapy should be continued for life unless there is evidence of immune recovery.

Primary options

ganciclovir: 5 mg/kg intravenously every 12 hours

and

foscarnet: 60 mg/kg intravenously every 8 hours, or 90 mg/kg intravenously every 12 hours

refractory/resistant infection

1st line – maribavir, foscarnet, cidofovir, or high-dose ganciclovir

Back
ACUTE
|
refractory/resistant infection
1st line – 

maribavir, foscarnet, cidofovir, or high-dose ganciclovir

Refractory or resistant cytomegalovirus (CMV) should be suspected in the presence of persistent or recurrent CMV viraemia and prolonged exposure to antivirals and tested for with genotypic resistance analysis.[51]

Treatment of these patients is complex and should be done in conjunction with a specialist.[1][51]​​​​​

Maribavir is the first-line option for post-transplant CMV infection that does not respond to available antiviral treatment (with or without genotypic resistance). In the US, maribavir is approved for treating adults and children (aged 12 years and older and weighing at least 35 kg). However, in Europe it is currently approved for adults only.

In the phase 3 SOLSTICE trial, maribavir demonstrated superior viral clearance compared with investigator-assigned therapy (valganciclovir/ganciclovir, foscarnet, cidofovir, or foscarnet plus valganciclovir/ganciclovir) in transplant recipients with refractory/resistant CMV infection (55.7% achieving CMV clearance at 8 weeks compared with 23.9%).[55]

In the AURORA trial, maribavir and valganciclovir were evaluated for managing initial asymptomatic CMV infections in patients following haematopoietic cell transplantation. Although maribavir did not achieve the targeted noninferiority for clearing CMV viraemia by the 8th week, it effectively maintained CMV suppression without disease progression up to the 16th week, similar to valganciclovir. Maribavir demonstrated a better safety profile with reduced cases of neutropenia and fewer treatment discontinuations due to adverse events, highlighting its utility as a preferred option for managing CMV in the early post-transplant period.[56]

There is a concern of the acquisition of resistance against maribavir in cases of refractory/resistant CMV infection manifesting with high viral loads or in cases of severe disease. In these cases, expert opinion suggests starting therapy with foscarnet, with a step down to maribavir after clinical improvement and once viral load has decreased. A clear viral load threshold for preferring the use of foscarnet has not been established.[57]

UL97-mutant CMV confers resistance to ganciclovir, and antiviral treatment for these patients typically involves the use of maribavir, foscarnet, and less commonly, cidofovir. Occasionally, higher than normal doses of ganciclovir may also be an option. Although maribavir targets UL97, cross-resistance with ganciclovir is uncommon. UL54-mutant CMV, which has a mutation in CMV DNA polymerase, may confer cross-resistance among ganciclovir, foscarnet, and cidofovir (depending on the exact site of the mutation), leading to more limited treatment options for these patients.

Reduction in immunosuppression should accompany antiviral therapy, to allow immune reconstitution and subsequent control of the virus by the immune system. Treatment should be determined and administered in a specialist setting.

Primary options

maribavir: children ≥12 years of age and ≥35 kg body weight and adults: 400 mg orally twice daily

Secondary options

foscarnet: consult specialist for guidance on dose

OR

cidofovir: consult specialist for guidance on dose

Tertiary options

ganciclovir: consult specialist for guidance on dose

congenital infection

1st line – oral valganciclovir or intravenous ganciclovir

Back
ACUTE
|
congenital infection
1st line – 

oral valganciclovir or intravenous ganciclovir

Oral valganciclovir is recommended for the treatment of newborns with moderate-to-severe, symptomatic congenital cytomegalovirus (CMV).[32][58][59]​​​​​ Intravenous ganciclovir is recommended as an alternative option for severe, symptomatic congenital infection, but is seldom used.[32][60][61]​​​

Valganciclovir and ganciclovir have been shown to prevent progression of hearing loss.[59][60][61]​ Therapy should be administered for 6 months, starting within the first month after birth.[32][58][59]​​​​ Prolonged treatment with valganciclovir results in modest long-term improvement in neurodevelopment and hearing.[59] Neutropenia is a frequent adverse event associated with ganciclovir.[60][61]

To date, there is no sufficient evidence for recommending treatment of neonates with asymptomatic or mild congenital CMV. Evidence from randomised trials to inform the initiation of antiviral therapy beyond the first month of life is also absent.[58]​ Several studies aiming to establish whether there is a benefit in treating neonates with isolated sensorineural loss, or in treating newborns beyond the first month of life, are ongoing.[58]

Primary options

valganciclovir: consult specialist for guidance on dosing

Secondary options

ganciclovir: consult specialist for guidance on dosing

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer