Increased human cytomegalovirus (HCMV) DNA load in peripheral blood leukocytes after lung transplantation correlates with HCMV pneumonitis

Background. Human cytomegalovirus (HCMV) reactivation and disease remain re latively common in lung transplant recipients (LTR) despite the use of ganc iclovir prophylaxis protocols for all HCMV at-risk patients. The specific a ims of this study were to (1) describe the HCMV DNA viral load in the perip heral blood leukocytes (PBL) of a cohort of LTR during the first 6 months a fter lung transplantation; (2) prospectively determine whether HCMV DNA vir al load predicts episodes of HCMV pneumonitis in LTR; and (3) study the eff ect of ganciclovir on HCMV viral load. Methods. Competitive polymerase chain reaction using an internal standard a nd fluorometric detection were used to quantitate HCMV DNA in the PBL of a cohort of 26 LTR monthly for the first 6 months after transplantation (145 samples). All patients were treated with standard triple immunosuppression, and ganciclovir prophylaxis was given to all at-risk LTR (donor or recipie nt HCMV seropositive) for at least 8 weeks after transplantation. Results. Thirteen episodes of histopathologically proven HCMV pneumonitis i n nine subjects occurred during follow-up with a wide intra- and intersubje ct variation in the HCMV DNA PBL levels. HCMV detection had a sensitivity o f 92% and specificity of 76% for HCMV pneumonitis (negative likelihood rati o, 9.5), whereas greater than 10-fold increases in HCMV DNA load had a spec ificity of 93% and sensitivity of 67% (positive likelihood ratio, 11), HCMV DNA detection had an adjusted odds ratio for HCMV pneumonitis of 107 (95% confidence interval, 14-821; P <0.005), In those with detectable HCMV DNA i n PBL (n=44), HCMV DNA levels were 4.4 (95% confidence interval, 1.2-16.8) times higher in those with HCMV pneumonitis than in those without HCMV pneu monitis. Although ganciclovir treatment was very effective in treating HCMV pneumonitis and suppressing HCMV DNA levels, thrice weekly ganciclovir pro phylaxis only partially controlled HCMV DNA levels and did not eliminate HC MV pneumonitis risk as three patients developed HCMV pneumonitis while on t his regimen. Conclusions, HCMV DNA detection, absolute levels, and relative change from baseline in the PBL of LTR correlate with HCMV pneumonitis episodes and may be a useful intermediate outcome measure of the efficacy of ganciclovir pr ophylaxis and treatment strategies.