Prophylactic Versus Preemptive Oral Valganciclovir for the Management of Cytomegalovirus Infection in Adult Renal Transplant Recipients

Abstract

Prophylaxis reduces cytomegalovirus (CMV) disease, but is associated with increased costs and risks for side effects, viral resistance and late onset CMV disease. Preemptive therapy avoids drug costs but requires frequent monitoring and may not prevent complications of asymptomatic CMV replication. Kidney transplant recipients at risk for CMV (D+/R−, D+/R+, D−/R+) were randomized to prophylaxis (valganciclovir 900 mg q.d. for 100 days, n = 49) or preemptive therapy (900 mg b.i.d. for 21 days, n = 49) for CMV DNAemia (CMV DNA level >2000 copies/mL in ≥ 1 whole blood specimens by quantitative PCR) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. More patients in the preemptive group, 29 (59%) than in the prophylaxis group, 14 (29%) developed CMV DNAemia, p = 0.004. Late onset of CMV DNAemia (>100 days after transplant) occurred in 11 (24%) randomized to prophylaxis, and none randomized to preemptive therapy. Symptomatic infection occurred in five patients, four (3 D+/R− and 1 D+/R+) in the prophylactic group and one (D+/R−) in the preemptive group. Peak CMV levels were highest in the D+/R− patients. Both strategies were effective in preventing symptomatic CMV. Overall costs were similar and insensitive to wide fluctuations in costs of either monitoring or drug.

Impact of Antiviral Preventive Strategies on the Incidence and Outcomes of Cytomegalovirus Disease in Solid Organ Transplant Recipients

“…A few randomized controlled trials have recently compared prophylaxis and preemptive therapy. However, Dþ/RÀ patients were not included (14) or represented only a minority of all patients included in these trials (10,11). Some studies showed a marked benefit of the preemptive approach in Dþ/RÀ patients (28,29), although recent studies have shown a similar or even higher incidence of CMV diseases compared to the use of antiviral prophylaxis (9,30).…”

“…Current guidelines recommend both approaches, although antiviral prophylaxis is generally preferred for high-risk patients (1,2). However, direct comparison of both strategies has been assessed only in a few small randomized controlled trials (10)(11)(12)(13)(14).…”

Easier Control of Late-Onset Cytomegalovirus Disease Following Universal Prophylaxis Through an Early Antiviral Immune Response in Donor-Positive, Recipient-Negative Kidney Transplants

“…Because EOD occurs mainly after a preemptive strategy, we believe that this strategy is not appropriate in D+RÀ patients and argue strongly for universal prophylaxis in these high-risk patients. Moreover, in na€ ıve D+/RÀ patients, universal prophylaxis is thought to hamper the development of a specific immune response, causing more late-onset CMV infections than the preemptive approach (3,39), with increased morbidity (10). This observation could argue for the choice of a preemptive strategy.…”

“…CMV incidence remains elevated in these patients, at between 16% and 37%, depending on the duration of preventive therapy (1,2). In one study directly comparing prophylactic and preemptive approaches, it was clearly demonstrated that late DNAemia occurs much more frequently in the prophylactic versus the preemptive setting (3,4). In addition, late DNAemia has been associated with poor prognosis, with a reduction in graft survival and higher patient mortality (5)(6)(7)(8)(9)(10).…”

A Case of Cytomegalovirus-Induced Arthritis after Lymphocyte-Depleting Therapy for Kidney Allograft Rejection

“…The patient may have benefited from a preemptive screening strategy, which has been recommended as an alternative to universal prophylaxis in kidney transplant recipients at risk for CMV infection [16,17]. While prophylaxis has been associated with superior graft and patient survival [18,19], as well as cost and quality of life benefits [20] compared to a preemptive strategy, the latter may be appropriate for patients at risk for CMV disease with contraindications to oral valganciclovir therapy [17,21].…”