Sandbox jyostna

• Cytomegalovirus treatment

• 1. Retinitis

• In HIV-infected adults

Ganciclovir IV, Valganciclovir PO, Foscarnet IV, Cidofovir IV AND Ganciclovir intraocular implant coupled with Valganciclovir.

• In HIV-infected infants and children

initial treatment (induction therapy): Ganciclovir IV for acquired CMV disease, including CMV retinitis and other end-organ disseminated CMV disease (e.g., colitis, esophagitis, CNS disease).

Note (1): Oral Valganciclovir, a prodrug of Ganciclovir, is one of the first-line treatments for HIV infected adults with CMV retinitis and is an option in older children who weigh enough to receive the adult dose and tablet formulation of Valganciclovir. The drug is well absorbed from the GI tract and rapidly metabolized to Ganciclovir in the intestine and liver.

Note (2): Valganciclovir oral solution has not been studied in pediatric patients for treatment of CMV retinitis, but consideration can be given to its use for transitioning from Ganciclovir IV to Valganciclovir oral to complete treatment and or for secondary prophylaxis once improvement in retinitis is noted.

• An alternative drug for treating CMV disease or for use in Ganciclovir-resistant CMV infections in HIV infected children : Foscarnet.

Note (1): Foscarnet used as suppressive therapy has been associated with increased length of survival relative to Ganciclovir in HIV-infected adults. Doses should be modified in patients with renal insufficiency.

Note (2): Cidofovir is effective in treating CMV retinitis in adults who are intolerant of other therapies.

Note (3): Combination therapy with Ganciclovir and Foscarnet delays progression of retinitis in certain patients in whom monotherapy fails and can be used as initial therapy in children with sight-threatening disease.

Note (4): Combination therapy also has been used for adults with retinitis that has relapsed on single-agent therapy.

• 2. In Transplant patients

• Preferred regimen: Valganciclovir

Note (1): Use of Valganciclovir to prevent infections in CMV seronegative recipients who receive organs from a seropositive donor and in seropositive receivers has been highly effective.

Note (2): Others suggest preemptive treatment when pt develops CMV antigenemia or positive PCR post-transplant.

• 3. Colitis, Esophagitis

• Preferred regimen (1): Valganciclovir 900 mg PO q24h.
• Preferred regimen (2): Valganciclovir 900 mg PO q12h for 14–21 days, then 900 mg PO q24h for maintenance therapy
• Alternative regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days ,Ganciclovir as with retinitis except induction period extended for 3–6 wks (No agreement on use of maintenance; may not be necessary except after relapse. Responses less predictable than for retinitis.), then Valganciclovir 900 mg PO q24h OR Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h for 14–21 days, then 90–120 mg/kg IV q24h OR Cidofovir 5 mg/kg IV for 2wks, then 5 mg/kg every other wk; each dose should be administered with IV saline hydration AND oral probenecid OR repeated intravitreal injections with Fomivirsen (for relapses only, not as initial therapy)

Note (1): Diagnosis by biopsy of ulcer base or edge with demonstration of CMV inclusions and other pathogen.

Note (2): Switch to oral Valganciclovir when PO tolerated & when symptoms not severe enough to interfere with absorption.

Note (3): Antiretroviral therapy is essential in long term suppression.

• 4. Pneumonia

• Preferred regimen: : Valganciclovir 900 mg PO q12h for 14–21 days, then 900 mg PO q24h for maintenance therapy
• Alternative regimen for retinitis: Ganciclovir 5 mg/kg IV q12h for 14–21 days, then Valganciclovir 900 mg PO q24h OR Foscarnet 60 mg/kg IV q8h or 90 mg/kg IV q12h for 14–21 days, then 90–120 mg/kg IV q24h OR Cidofovir 5 mg/kg IV for 2wks, then 5 mg/kg every other wk; each dose should be administered with IV saline hydration AND oral probenecid.

Note (1): CMV pneumonia seen predominantly in transplants (esp. bone marrow), rare in HIV.

Note (2): Treat only when histological evidence resent in IDS patients and other pathogens not identified.

Note (3): High rate of CMV reactivation in immunocompetent ICU patients; prolonged hospitalizations and increased mortality.

Note (4): In bone marrow transplant patients, combination therapy with CMV immune globulin. In bone marrow transplant patients, serial measure of pp65 antigen was useful in establishing early diagnosis of CMV interstitial pneumonia with good results if Ganciclovir was initiated within 6 days of antigen positivity.

• 5. Encephalitis, Ventriculitis

Note: Treatment not defined, but should be considered the same as retinitis. Disease may develop while taking Ganciclovir as suppressive therapy.

• 6. Lumbosacral polyradiculopathy

• Preferred regimen: Ganciclovir, as with retinitis. Foscarnet 40 mg/kg IV q12h another option.Switch to Valganciclovir when possible.

Note (1): Diagnosis by CMV DNA in CSF.

Note (2): Suppression continued until CD4 remains >100/mm3 for 6 months.

Note (3): About 50% will respond; survival increases (5.4wks to 14.6wks).

• 7. Mononeuritis multiplex

Note (1): Due to vasculitis and may not be responsive to antiviral therapy

Note (2): Marked decrease in HIV associated CMV infections & death with Highly Active Antiretroviral Therapy. Initial treatment should optimize HAART.

Note (3): Primary prophylaxis not generally recommended. Preemptive therapy in patients with increased in CMV DNA titers in plasma and CD4 <100/mm3. Recommended by some is Valganciclovir 900 mg PO q24h.

Note (4): Risk for developing CMV disease correlates with quantity of CMV DNA in plasma is each log 10. increase associated with 3.1-fold increase in disease.

• 8. Specific considerations

Note (1): Currently, no therapies are available for the treatment of maternal or fetal CMV infection.

Note (2): Antiviral medications such as Ganciclovir, Valganciclovir and Foscarnet are approved by the U.S. Food and Drug Administration (FDA) only for treatment of patients with acquired immunodeficiency syndrome (AIDS) or organ transplants.

• Prevention

• 1. Prevention of opportunistic infections in human stem cell transplantation (HSCT) by CMV (Recipient with CMV positive or Donor with CMV positive /Recipient with negative CMV)

• Preemptive therapy: Monitor ≥1 wk (days 10-100) CMV viremia by PCR or CMV-antigenemia and start treatment if positive. Traditional approach was to use Ganciclovir 5 mg/kg IV q12h for 7-14 days, then 5 mg/kg IV q24h 5 days/wk to the longer of: d 100 or ≥3 wks.

Note (1): More recently, Valganciclovir used more often in those who can take oral medications. Continue therapy until viral load negative (preferably twice).

Note (2): One study found Valganciclovir 900 mg po bid comparable to Ganciclovir 5 mg/kg iv bid in preemptive regimen

Note (3): Valganciclovir 900 mg po bid for 2 wks, then 900 mg PO q24h for ≥7 days after negative viral assay, was effective

Note (4): Preemptive regimen of Valganciclovir 900 mg po bid×2 wks, then 450 mg po bid, was effective OR

• Alternatively Prophylaxis approach (for high-risk pts or when CMV detection tests not rapidly available): From engraftment to day 100, ganciclovir 5 mg/kg IV q12h for 7 days, then 5 mg/kg IV q24h 5 to 6 days per week.

• 2. Prevention of opportunistic infections in Solid organ transplant (SOT) by CMV (Recipient with CMV positive or Donor with CMV positive /Recipient with negative CMV)

• 2.1 Kidney, Kidney/Pancreas, Heart

• Preferred regimen: Valganciclovir 900 mg PO q24h; start by day 10 and continue to at least day 100.

• 2.2 Liver

• Preferred regimen: Ganciclovir 5 mg/kg IV qd or Ganciclovir 1 gm PO tid; start by day 10 and continue to at least day 100. Or, with caution, Valganciclovir.

• 2.3 Lung

• Preferred regimen: Ganciclovir 5 mg/kg iv q12h for 5-7 days, then Valganciclovir 900 mg po q24h for 6 mos (or at least 3 months).

Note (1): With antiviral prophylaxis, onset of CMV is appearing later; optimal duration of prophylaxis under study.

Note (2): Valganciclovir does not have FDA indication for CMV prevention in liver or lung transplantation, but commonly used.

Note (3): In selected cases, some institutions add CMV immune globulin to antiviral drug in high risk cases. Regimen for lung, heart, liver, pancreas: 150 mg/kg within 72h of transplant and at 2, 4, 6 & 8 weeks post-transplant; then 100 mg/kg at weeks 12 & 16.

• 3. Post treatment suppression for retinitis (prophylactic) if CD4 count <100/mm3

• Preferred regimen: Valganciclovir 900 mg PO q24h.

Note (1): Discontinue if CD4 >100/mm3 for 6 months on ART.

Note (2): Patients who discontinue suppression therapy should undergo regular eye examination for early detection of relapses.