A Direct and Indirect Comparison Meta-Analysis on the Efficacy of Cytomegalovirus Preventive Strategies in Solid Organ Transplant

Background. Prophylactic and preemptive strategies are used to prevent cytomegalovirus (CMV) infections after solid organ transplant. We assessed the safety and efficacy of both strategies for CMV prevention. Methods. A DerSimonian and Laird random-effects model was used for pooling the data, and Q statistic and I-2 methods were used to assess statistical heterogeneity. Results. Twenty studies (2744 patients) were selected for the direct analysis and 20 studies (2544 patients) for the indirect analysis. The odds of CMV syndrome (odds ratio [OR] = 1.10; 95% confidence interval [CI], .60-2.03; P = .757; Q = 18.55; I-2 = 51.5%) and disease (OR = 0.77; 95% CI, .41-1.47; P = .432; Q = 32.71; I-2 = 45.0%) were not significantly different between strategies. The odds of developing late-onset CMV infections were higher for the prophylactic compared to the preemptive strategy (OR = 6.21; 95% CI, 2.55-15.20; P < .0001; Q = 9.66; I-2 = 37.9%). The odds of CMV viremia were lower for prophylaxis (OR = 0.42; 95% CI, .24-.74; P = .003; Q = 48.10; I-2 = 75.1%) than preemptive therapy. No differences between strategies were noted for graft loss (OR = 0.88; 95% CI, .37-2.13; P = .779; Q = 13.03, I-2 = 38.6%), graft loss censored for death (OR = 0.73; 95% CI, .17-3.21; P = .679; Q = 4.48; I-2 = 55.3%), acute rejection (OR = 0.93; 95% CI, .70-1.24; P = .637; Q = 12.99; I-2 = 7.6%), or mortality (OR = 0.80; 95% CI, .56-1.14; P = .220; Q = 8.76; I-2 = 0%). The odds for other infections (herpes simplex virus, varicella zoster virus, bacterial and fungal infections) did not significantly differ between strategies. Leukopenia (OR = 1.97; 95% CI, 1.39-2.79; P = .0001; Q = 7.10; I-2 = 0%) and neutropenia (OR = 2.07; 95% CI, 1.13-3.78; P = .018; Q = 6.77; I-2 = 11.4%) were more frequent with prophylaxis than with the preemptive strategy. The results of direct and indirect comparisons were consistent. Conclusions. Prophylaxis was associated with less early posttransplant viremia, but significantly more late-onset CMV infections and side effects (leukopenia and neutropenia) than the preemptive strategy. Both preventive strategies showed similar efficacy in preventing CMV syndrome and disease, with no differences regarding rejection, graft loss, death, or opportunistic infections.