CMV Prophylaxis in High-Risk Renal Transplant Patients (D+/R-) by Acγclovir with or without Hyperimmune (CMV) Immunoglobulins: A Prospective Study

Abstract

In this prospective randomized study including 28 patients, we show that, in cytomegalovirus (CMV)-seronegative renal transplant recipients (R-) receiving a CMV-seropositive graft (D+), high doses of acyclovir (ACV, i.e. 3,200 mg/day) during the first 3 months after transplantation were as efficient as hyperimmune CMV immunoglobulins (CMV Igs) plus high doses of ACV regarding the prophylaxis of CMV primoinfection. Fifty-four percent of the patients in the ACV arm and 50% in the other arm presented at least one episode of viremia (n.s.). The incidence of CMV disease was 31% in the ACV group and 20% in the ACV + CMV Ig group (n.s.). By comparison with historical controls (no prophylaxis), we found that ACV with or without CMV Ig significantly delayed and significantly decreased the rate of CMV disease, although the severity score was not statistically different. Moreover, high doses of ACV were far less expensive than their combination with hyperimmune CMV Igs. Thus, until oral ganciclovir is available for the prophylaxis of primary CMV infection in renal transplant patients, we recommend the use of high doses of ACV for the first 3 months after transplantation in high-risk renal transplant patients, i.e. D+/R-.

Low‐dose valaciclovir and cytomegalovirus immunoglobulin to prevent cytomegalovirus disease in high‐risk renal transplant recipients

“…The efficacy of low‐dose valaciclovir (3000 mg/day) was suggested by two small retrospective renal transplant studies, where the incidence of CMV disease was 8.5% at 6 months 14 and 24% at 3 years, 15 respectively. CMVIg, administered as monotherapy or in combination with antiviral agents, also reduces the incidence of CMV disease by up to 75% in renal transplant recipients 16–19,27–29 and a meta‐analysis of CMVIg in SOT showed a significant reduction in CMV disease, CMV‐related deaths and all‐cause mortality 17 …”

“…A study by Opelz et al ., 27 showed that CMV prophylaxis (with aciclovir, ganciclovir or CMVIg) improved graft survival and reduced rejection in D+/R− patients. Other reported benefits of CMV prophylaxis include a reduction in opportunistic infections including Pneumocystis jeroveci pneumonia 3,28,30 . One retrospective multicentre analysis also showed that CMVIg was associated with a decrease in the incidence of post‐transplant lymphoproliferative disease in the first year post transplant 27 …”

CMV‐hyperimmune globulin for preventing cytomegalovirus infection and disease in solid organ transplant recipients: a meta‐analysis

“…Full-text assessment of 15 potentially eligible articles identified 11 trials including 698 patients (Table 1). Studies compared CMVIG with placebo or no treatment (7,(9)(10)(11)(12)(13)(14)(15). Two additional trials compared CMVIG with acyclovir (16,17).…”

Prevention of infections in solid organ transplant recipients

“…Acyclovir at high doses (800 mg four times per day) administered for the first 3 months post‐transplant has been successful preventing CMV disease in renal transplant recipients at risk for primary CMV infection (D+R−) ( 72–74). The addition of CMV hyperimmune globulin in these cases has been advocated ( 75–77). A recent unpublished study (M. Vaugar, Glaxo Wellcolue) indicates that the valine ester of acyclovir (valacyclovir) prevents CMV disease not only in the low, but also in high‐risk (D+/R−) renal transplant recipients.…”