Anti-herpesvirus prophylaxis, pre-emptive treatment or no treatment in adults undergoing allogeneic transplant for haematological disease: systematic review and meta-analysis

Abstract

BackgroundHerpesviridae infections incur significant morbidity and indirect effects on mortality among allogeneic haematopoietic cell transplant (allo-HCT) recipients. ObjectivesTo study the effects of antiviral prevention strategies among haemato-oncological individuals undergoing allo-HCT. Data sourcesCochrane Central Register of Controlled Trials, MEDLINE, Embase and LILACS. We further searched for conference proceedings and trial registries. Study eligibility criteriaRandomized controlled trials (RCTs). ParticipantsAdults with haematological malignancy undergoing allo-HCT. InterventionsAntiviral prophylaxis versus no treatment/placebo or pre-emptive treatment and pre-emptive treatment versus prophylaxis with the same agent. MethodsRandom-effects meta-analysis was conducted computing pooled risk ratios (RR) with 95% CI and the inconsistency measure (I2). The certainty of the evidence was appraised by GRADE. ResultsWe included 22 RCTs. Antiviral prophylaxis reduced all-cause mortality (RR 0.83, 95% CI 0.7–0.99; 15 trials, I2 = 0%), cytomegalovirus (CMV) disease (RR 0.54, 95% CI 0.34–0.85; n = 15, I2 = 20%) and herpes simplex virus (HSV) disease (RR 0.29, 95% CI 0.2–0.43; n = 13, I2 = 18%) compared with no treatment/placebo or pre-emptive treatment, all with high-certainty evidence. Furthermore, antivirals reduced HSV infection, CMV pneumonitis, CMV infection and varicella zoster virus disease. Anti-CMV prophylaxis (+/– pre-emptive treatment) compared with pre-emptive treatment alone reduced non-significantly all-cause mortality (RR 0.78, 95% CI 0.6–1.02; n = 8, I2 = 0%), CMV disease (RR 0.47, 95% CI 0.23–0.97; n = 9, I2 = 30%) and HSV disease (RR 0.41, 95% CI 0.24–0.67; n = 4, I2 = 0%) with high-certainty evidence, as well as CMV and HSV infections. Antiviral prophylaxis did not result in increased adverse event rates overall or more discontinuation due to adverse events. ConclusionsAntiviral prophylaxis directed against herpesviruses is highly effective and safe, reducing mortality, HSV and CMV disease, as well as herpesvirus reactivations among allo-HCT recipients. Anti-CMV prophylaxis is more effective than pre-emptive treatment alone with respect to HSV and CMV disease and infection.