Antiviral drugs against CMV: Four antiviral agents have been approved for treatment of CMV infections (Table 1) and three novel drugs are currently under evaluation.

Ganciclovir (GCV): It is an acyclic guanosine analog. It gets converted to its active form ganciclovir triphosphate by the viral phosphatase coded by gene UL97. Ganciclovir triphosphate selectively inhibits CMV DNA polymerase. It is given either alone or in combination with CMV immunoglobin in severe cases. Majority of the patients treated with ganciclovir show a good response.

Resistance may develop in patients treated for more than 3 months. Mutation in the gene CMV UL97 and less commonly in UL54 is responsible for development of GCV resistance. Myelosuppression leading to leukopenia is the most common manifestation seen with IV ganciclovir.

Valganciclovir: It is a prodrug of ganciclovir. On oral administration, the drug gets hydrolyzed to ganciclovir by the esterase present in the intestine and liver. The oral bioavailability of the drug is 60–70%. The oral valganciclovir of 900 mg once daily is considered to be same as IV ganciclovir of 5 mg/kg once daily. It is considered to be as equally effective of IV ganciclovir therapy for CMV induction (treatment) and maintenance therapy

Dose regimen:

 IV Ganciclovir:

5 mg/kg twice daily

Valganciclovir:

900 mg/twice daily.

Foscarnet (phosphonoformic acid): It inhibits DNA polymerase and as it does not require activation by phosphorylation it is active against ganciclovir resistant CMV. However, it is a highly toxic drug that includes renal dysfunction, hypokalemia and hypomagnesemia, hypo- or hyperphosphatemia, hypo- or hypercalcemia. Foscarnet is available only in intravenous formulation.

Dose regimen:

• 90 mg/kg, twice daily × 2–3 weeks for induction therapy.

Cidofovir: This is a cytosine nucleotide analog. It gets phosphorylated to its active diphosphate form which is independent of viral enzyme. It is used mainly in the ganciclovir resistant cases. Renal toxicity is the major adverse effect.

Dose regimen:

• 5 mg/kg/week × 2–3 weeks for induction therapy.

Newer agents: Letermovir, maribavir and brincidofovir are the novel antiviral compounds which have been evaluated for CMV prophylaxis in transplant recipients.

Letermovir: This is a 3,4-dihydroquinazoline 4-yl acetic acid derivative. It acts by terminating the CMV viral terminase complex and inhibits the processing and packaging steps in viral replication. Unlike ganciclovir and valganciclovir, it does not have any hematological toxicity, hence better tolerated. In phase 3 randomised control trial in HCT patients, significant reduction in CMV infection was observed with letermovir as compared to standard pre-emptive therapy (37.5% vs 60%). Similar result has been reported in SOT patients. It has been suggested that letermovir may decrease the mortality by preventing or delaying the development of CMV disease. The major limitation of this drug is its potential low barrier to develop resistance, no activity against other herpes viruses.

Maribavir and brincidofovir are two oral drugs currently under different phases of clinical trial for prophylaxis and treatment of CMV disease in transplant recipients.

Antiviral treatment for HCMV disease is recommended in the following conditions:

 a. Prevention and treatment of HCMV disease in transplant recipients (SOT and HSCT).

 b. Prevention and treatment of HCMV disease in HIV patients.

c. Treatment of congenital HCMV disease.

The approved antiviral drugs used for HCMV disease prevention and treatment are listed in Table 1.

Table1. Drugs used for prophylaxis of HCMV disease

Two strategies are commonly employed for prevention of HCMV disease: Prophylaxis and pre-emptive therapy (Table 2).

Table2. Therapeutic strategies for prevention of HCMV disease in transplant recipients

Recommendation of International Consensus group for CMV disease prevention in SOT patients:

• Either prophylaxis or pre-emptive therapy can be employed in:

– D+/R– kidney/liver transplant recipients

.– All seropositive recipients (R+) for kidney/liver/heart transplantation.

 • Prophylaxis is preferred over pre-emptive strategy in:

– D+/R– heart and lung transplant recipients.

– Patients with potent immunosuppressive therapy/antilymphocyte therapy/ and HIV.

Recommendation of expert panel for prevention of CMV infection in HSCT patients: It is recommended to adapt either prophylaxis or pre-emptive therapy for all CMV seropositive recipients and D+/R HSCT patients from the day of engraftment till 100 days post-transplantation. Intravenous ganciclovir is recommended for allogenic HSCT recipients.

Antiviral treatment is also recommended to HIV patients with HCMV infection and newborns with signs of congenital CMV infection with ganciclovir.

اخر الاخبار

اخبار العتبة العباسية المقدسة

شعبة الخطابة النسوية تعقد اجتماعًا تحضيريًّا للمتطوعات خلال زيارة الأربعين

ملاكات الحزام الأخضر الجنوبي تشرع بجني التمور والمحاصيل الخضرية من واحاته

المجمع العلمي يقيم أنشطة قرآنية متنوعة في محافظات عدة

قسم المشاريع ينجز صبّ أكثر من 200 م³ من الخرسانة في المساحات الإضافية لصحن أم البنين (عليها السلام)

المزيد

الآخبار الصحية

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تحذير من عادة شائعة بين الركاب تنقل "عدوى مهددة للحياة" ؟

دراسة علمية تكشف مفاجأة حول الأسباب الحقيقية للسمنة

دراسة: الأطباء يتجاهلون "سببا شائعا" لارتفاع ضغط الدم

المزيد

الآخبار التكنلوجية

لأول مرة.. فيديو يرصد ولادة كوكب !

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تسريبات جديدة تكشف موعد إصدار آيفون 17 ومواصفاته

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المزيد

مواضيع ذات صلة

Diagnosis of Cytomegalovirus

Clinical Manifestations of Cytomegalovirus

The Viral Genome

Human Immunodeficiency Virus

Viral Pathogenesis

VIRUSES

Human Cytomegalovirus

Influenza Virus Infections in Humans

Varicella-Zoster Virus

Adenovirus Coinfection with SARS-CoV-2

Genetic Polymorphisms susceptibility to SARS-CoV-2

Acute viral hepatitis