Risky Business: Prophylaxis and Treatment of Cytomegalovirus in the Transplantation Setting

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Question 1
Which preemptive strategy is most appropriate as initial treatment for a first episode of cytomegalovirus (CMV) reactivation in hematopoietic stem cell transplant (HSCT) recipients with normal leukocyte count and adrenal function?
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Correct Answer: C
Rationale: 
Preemptive therapy for late CMV disease should include preemptive therapy with valganciclovir (900 mg twice daily) if CMV DNA is more than 1000 copies/mL. Induction dosing should be continued until viral load declines, at least 1 week. Treat with maintenance dose (900 mg/day) until viral load is undetectable. Boeckh M, et al. Blood. 2009;113(23):5711-9.

Question 2
Maribavir, an investigational anti-CMV agent:
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Correct Answer: B
Rationale: 
Maribavir is an oral benzimidazole L-riboside inhibitor of the CMV UL97 kinase. At higher doses, it has been used as salvage therapy for drug-resistant CMV infection, with mixed results. A phase 2 trial of maribavir (400, 800, or 1200 mg bid) for salvage treatment of refractory and resistant CMV infection has been completed, with indications of success in that approximately 67% achieved clearance of viral DNA within 6 weeks, but infection recurred in approximately 35% of those who cleared. Salvage efficacy did not vary significantly among the 3 doses tried. Kotton CN, et al. Transplantation. 2018;102(6):900-31; Papanicolaou G, et al. Presented at: IDWeek 2016; October 26-30, 2016; New Orleans, LA. Abstract 78.

Question 3
Which of the following is true regarding the current recommended approaches for CMV prevention in solid organ transplantation (SOT)?
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Correct Answer: C
Rationale: 
The 2018 Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation has the following recommendations:

• For D+/R−, we recommend the use of either prophylaxis or preemptive therapy after kidney and liver transplant (strong, high). 
• Either universal prophylaxis or preemptive therapy for prevention of CMV disease (strong, high). 
• For D+/R− kidney recipients, prophylaxis for 6 months is preferable (strong, high). 
• Between 6 and 12 months of prophylaxis is recommended for D+/R− lung transplant recipients (strong, moderate).

Kotton CN, et al. Transplantation. 2018;102(6):900-31.

Question 4
Which of the following is true regarding letermovir as an anti-CMV therapy in transplant recipients?
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Correct Answer: B
Rationale: 
Letermovir inhibits the terminase complex by binding to UL56, UL51 indicated for prophylaxis of CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic HSCT. Marty FM, et al. N Engl J Med. 2017;377(25):2433-44.

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