Sandbox jyostna

• 1. Retinitis

• Preferred regimen (1) for immediate sight-threatening lesions: Ganciclovir intraocular implant AND Valganciclovir 900 mg PO q24h.
• Preferred regimen (2) for peripheral lesions: 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 OR repeated intravitreal injections with Fomivirsen (for relapses only, not as initial therapy)

Note (1): Most common cause of blindness in AIDS patients with <50/mm3 CD4 counts is Cytomegalovirus.

Note (2): 19/30 pts (63%) with inactive CMV retinitis who responded to HAART (increase of ≥60 CD4 cells/mL) developed immune recovery vitreitis (vision decreases and floaters with posterior segment inflammation vitreitis, papillitis & macular changes) an average of 43 wks after teatment started.

Note (3): Corticosteroid treatment decreases inflammatory reaction of immune recovery vitreitis without reactivation of CMV retinitis, either periocular Corticosteroids or short course of systemic Steroid.

Note (4): Differential diagnosis is HIV retinopathy, herpes simplex retinitis, varicella-zoster retinitis (rare, hard to diagnose).

Note (5): Valganciclovir PO equal to Ganciclovir IV in induction of remission: Cannot use Ganciclovir ocular implant alone as approx. 50% risk of CMV retinitis other eye at 6 months and 31% risk visceral disease. Risk decreases with systemic treatment but when contralateral retinitis does occur, Ganciclovir-resistant mutation often present. Concurrent systemic treatment recommended.

Note (6): Because of unique mode of action, Fomivirsen may have a role if isolates become resistant to other therapies.

Note (7): Retinal detachments 50–60% within 1 year of diagnosis of retinitis.

Note (8): Equal efficacy of IV Ganciclovir and Foscarnet. Ganciclovir avoids nephrotoxicity of Foscarnet; Foscarnet avoids bone marrow suppression of Ganciclovir. Although bone marrow toxicity may be similar to Ganciclovir. Oral Valganciclovir should replace both.

• Post treatment suppression (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.

• 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

Dx by biopsy of ulcer base/edge  with demonstration of CMV inclusions & other pathogen.

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.

Valganciclovir also likely effective.

Switch to oral Valganciclovir when PO tolerated & when symptoms not severe enough to interfere with absorption.

Antiretroviral therapy is essential in long term suppression.

• 4. Encephalitis, Ventriculitis

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

• 5. 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).

• 6. Mononeuritis multiplex

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

• 7. 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.

Cytomegalovirus (CMV)

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

Primary prophylaxis not generally recommended. Preemptive therapy in patients with increased in  CMV DNA titers in plasma & CD4 <100/mm3. Recommended by some: valganciclovir 900 mg po q24h. Authors rec. primary prophylaxis be dc if response to HAART with incerase in CD4 >100 for 6 months. 

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

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.

Prevention of opportunistic infections in Solid organ transplant (SOT) by CMV (Recipient with CMV positive or Donor with CMV positive /Recipient with negative CMV) Kidney, Kidney/Pancreas, Heart Preferred regimen: Valganciclovir 900 mg PO q24h; start by day 10 and continue to at least day 100. 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. 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.

Currently, no therapies are available for the treatment of maternal or fetal CMV infection. 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.