Organism-Specific Therapeutic Regimens

Organism-specific therapeutic and prophylactic regimens for cytomegalovirus (CMV) infection are provided below, including those for patients with HIV-associated CMV retinitis;^{[1, 2, 3]}those with pneumonia, hepatitis, and gastrointestinal (GI) CMV infection; and those who have undergone transplant procedures.^{[4, 5, 6]}

Retinitis in patients with HIV infection

See the list below:

Initial induction therapy followed by maintenance therapy
Therapy is continued until immune reconstitution occurs

Preferred regimen:

Ganciclovir intraocular implantplus
Valganciclovir 900 mg PO BID for 21d, then 900 mg/day PO

Alternative regimens:

Ganciclovir 5 mg/kg IV q12h for 14d, then ganciclovir (5 mg/kg IV once daily or 6 mg/kg IV once daily for 5d/wk) or valganciclovir 900 mg/day PO or
Foscarnet 90 mg/kg IV q12h for 14d, then 90 mg/kg IV daily or
Cidofovir 5 mg/kg IV once weekly for 2wk, then 5 mg/kg IV once weekly

Pneumonia, hepatitis, GI CMV infection

Preferred regimens:

Valganciclovir 900 mg PO BID for 14-28d or
Ganciclovir 5 mg/kg IV q12h for 14-28d
In transplant patients, therapy is continued until clearance of viremia is documented

Alternative regimens:

Foscarnet 90 mg/kg IV q12h for 14-28d or
Cidofovir 5 mg/kg IV once weekly for 2wk, then 5 mg/kg IV once every 2wk or
Leflunomide 100 mg/day PO (not approved by the US Food and Drug Administration [FDA] for this indication)^[7]or
CMV IV immune globulin (150 mg/kg twice weekly for 2 wk, then weekly for 4wk) should also be given for pneumonitis in hematopoietic cell transplant (HCT) recipients or for refractory CMV infection in any setting

Posttransplant prophylaxis

Solid-organ transplant:

Valganciclovir 900 mg/day PO for 3-6mo after transplant or
Ganciclovir 5 mg/kg IV daily for 3-6mo after transplant

HCT:

Ganciclovir 5 mg/kg IV q12h for 5-7d beginning at engraftment, then 5 mg/kg IV once daily until 100d after transplant or
Foscarnet 60 mg/kg IV q12h for 7d, then 90-120 mg/kg IV once daily until 100d after transplant or
Valganciclovir 2 g PO TID until 100d after transplant

Posttransplant preemptive treatment

See the list below:

Preemptive treatment is an alternative to prophylaxis
Preemptive treatment requires frequent (once- or twice weekly) monitoring for evidence of CMV replication on antigen assay or quantitative polymerase chain reaction (PCR)
If viremia is detected, begin induction treatment; various centers use different protocols once viremia is suppressed

Additional considerations

See the list below:

Ganciclovir dosing must be adjusted in renal failure – For a creatinine clearance (CrCl) of 50-79 mL/min, the daily dose is reduced by 50%; for CrCl 25-49 mL/min, by 75%; for CrCl 10-24 mL/min, by 87.5%
Valganciclovir dosing must be adjusted in renal failure – For CrCl 40-59 mL/min, the daily dose is reduced by 50%; for CrCl 25-39 mL/min, by 75%; for CrCl 10-24 mL/min, by 87.5%
Foscarnet dosing must be adjusted in renal failure – For CrCl 72-98 mL/min, the daily dose is reduced by 22%; for CrCl 58-71 mL/min, by 45%; for CrCl 43-57 mL/min, by 56%; for CrCl 36-42 mL/min, by 67%; for CrCl 29-35 mL/min, by 72%; for CrCl < 29mL/min, foscarnet is not recommended
Cidofovir dosing is complicated; refer to manufacturer’s package insert
Toxicity may be the limiting factor for the administration of ganciclovir (neutropenia), valganciclovir (neutropenia), foscarnet (nephrotoxicity), and cidofovir (nephrotoxicity)
Diagnostic modalities include quantitative CMV DNA PCR (preferred in transplant settings), antigen assay, viral culture, and histopathology (intranuclear inclusions)
CMV resistance mutations should be suspected in patients who initially respond to anti-CMV treatment and subsequently develop an increasing viral load despite compliance with drug therapy; they should also be suspected if the patient’s condition deteriorates on ganciclovir therapy^[8]