Safety and Effectiveness of Low-Dose Valganciclovir Prophylaxis in Cytomegalovirus Seropositive Lung Transplant Recipients.

OBJECTIVES

Cytomegalovirus (CMV) predisposes lung transplant (LTx) recipients to acute rejections and chronic lung allograft dysfunction (CLAD). Guidelines recommend standard-dose valganciclovir (VGCV, 900 mg daily) prophylaxis, while evidence for low-dose VGCV (450 mg daily) in CMV seropositive recipients remains limited. We evaluated the efficacy and safety of low-dose VGCV prophylaxis in this population.

METHODS

We analysed 137 adult CMV seropositive primary LTx recipients receiving triple-drug immunosuppression without induction therapy. Recipients received low-dose VGCV (450 mg daily for ≥6 months), or standard-standard dose (900 mg daily for ≥6 months), if > 80% of the prophylaxis period was completed at the respective dose. Routine CMV monitoring was performed during prophylaxis and 3 months after discontinuation.

RESULTS

Of 120 eligible seropositive LTx recipients, 97 (80.8%) received low-dose and 23 (19.2%) received standard-dose VGCV with median durations of 272 and 246 days, respectively. Seventeen recipients (12%) with mixed dosing were excluded. One patient in each group discontinued prophylaxis due to severe leucopenia. Breakthrough CMV-DNAemia occurred in 3.1% of low-dose patients. Post-prophylaxis CMV episodes were common but occurred independently of VGCV dose or duration. No VGCV resistance was detected. Leucopenia was frequent and similarly unrelated to dose or duration. Rates of acute rejections (P = .358) or overall survival (P = .889) were similar, while low-dose VGCV prophylaxis was associated with improved CLAD-free survival (HR 2.30, 95% CI 1.33-3.97, P = .003).

CONCLUSIONS

In CMV-seropositive adult LTx recipients without induction therapy, low-dose VGCV prophylaxis was as safe and effective as standard-dose prophylaxis and was associated with superior CLAD-free survival. Future randomized clinical trial is warranted.