The case for cytomegalovirus prophylaxis in solid organ transplantation

Abstract

Cytomegalovirus prevention strategies have been debated for the past decade. This review argues in favour of the prophylaxis strategy. Clinical trials comparing prophylaxis to pre-emptive therapy have, thus far, had insufficient power to differentiate strategies, especially with regard to the indirect effects of CMV. From meta-analyses, prospective trials, observational studies, and case control studies, there is evidence that prophylaxis prevents cytomegalovirus infection and disease, reduces the indirect effects of cytomegalovirus, including organ rejection and transplant associated, all cause mortality as well as opportunistic infection, and even bacteremia as well as post transplant lymphoproliferative disease. Prophylaxis has also been shown to be cost effective. One must recognise that with the current prophylaxis regimens employed for 3 months post-transplantation, late onset cases of cytomegalovirus disease may occur. Cytomegalovirus replication monitoring may be necessary after cessation of prophylaxis, especially in the high risk cytomegalovirus seropositive donor to cytomegalovirus seronegative recipient. Future trials with longer periods of prophylaxis are being undertaken.

Human cytomegalovirus DNA replication: antiviral targets and drugs

“…Although approximately 5-10% of congenitally infected infants have symptomatic disease, associated with microcephaly, intracranial calcifications, hearing loss and physical and mental defects, the majority of the newborn children that will further develop HCMVassociated diseases appear to be normal at birth [3]. Antiviral drugs have been developed and employed for either prophylactic or pre-emptive therapies and for direct treatment for HCMV disease (discussed in References [4,5]). Five compounds have been currently licensed to treat established HCMV infections-ganciclovir (GCV), its oral prodrug valganciclovir, foscarnet (FOS), cidofovir (CDV) and fomivirsen.…”

Prophylaxis Versus Preemptive Anti-cytomegalovirus Approach for Prevention of Allograft Vasculopathy in Heart Transplant Recipients

“…8 Whereas universal prophylaxis almost completely suppresses CMV replication in the early post-transplant phase (but also exposes a large number of patients to drug toxicity and may select drug-resistant CMV strains), the preemptive strategy allows a period of unopposed sub-clinical CMV replication (but significantly reduces the number of patients receiving the anti-viral drug). 9,10 In practice, both approaches appear to be effective for prevention of the direct effects of acute CMV infection (i.e., CMV syndrome or CMV disease). 11,12 However, data from two recent randomized studies of kidney transplant recipients suggest that prophylaxis may be superior to pre-emption in preventing indirect consequences of CMV in terms of lower incidence of acute rejection 13 and better 4-year graft survival, with a similar drug safety profile.…”

Long-Term Outcomes of CMV Disease Treatment with Valganciclovir Versus IV Ganciclovir in Solid Organ Transplant Recipients

“…Blood samples were drawn in EDTA vacutainers at the following time points: days 0, 3,7,10,14,17,21,28,35,42 (21,(27)(28)(29)(30)(31)(32).…”