The Role of Quantitative Blood PCR in the Management of Congenital Cytomegalovirus Infection
The role of quantitative blood PCR (qPCR) in the management of congenital CMV infection has not yet been determined. The objective of this study was to determine the time to undetectable viral load (uVL) among infants treated with oral valganciclovir (VGCV) for congenital CMV infection.
All cases of congenital CMV diagnosed and treated between 2003 and 2013 at Centre Hospitalier Universitaire Sainte-Justine were identified retrospectively through the laboratory and clinical database. Cases were included for analysis if at least two blood qPCRs were done at any time after diagnosis while on treatment. CMV viral loads in QIAamp extracted DNA blood samples were estimated with an in-house qPCR method using TaqMan® MGB Hydrolysis probes/primers designed for UL83 gene and performed on a ABI 7500 platform. Treatment start time was at the discretion of the consultant physician, and treatment was stopped when qPCR became undetectable. Survival analysis was used to determine time to uVL and factors associated with a more rapid decline.
27 cases of congenital CMV were identified during the study period. Among them, only 9 of the treated infants had follow-up qPCRs; 2 received sequential IV and oral therapy, 7 received oral VGCV alone. Mean dose of VGCV was 15.2 mg/kg/dose (range 8.7-17.1 mg/kg/dose). Median initial qPCR was 79 460 copies/ml (IQR 12 1333- 203 525), and mean time to uVL was 199 days (range 30-450 days). After 6 months of treatment, only 44% (95% CI 20.0-79.6) had achieved uVL. This increased to 70.4% at 9 months (95% CI 39.0-94.8) and 85% (95% CI 53.0-99.0) 12 months after treatment was started. Infants were more likely to attain uVL if their initial viral load was <100 000 copies/ml (HR 1.99, p=0.51), initiated treatment at <7 days of life (HR 4.46, p=0.18), and initiated sequential IV then oral vs. oral therapy alone (HR 2.31, p=0.36), though none of these differences were statistically significant.
The use of serial qPCR may be a useful tool to monitor CMV disease activity and to guide treatment decisions in congenital CMV infection. Our results suggest that the recommended treatment duration of 6 weeks to 6 months may be too short to achieve an uVL in infants. Larger longitudinal studies are needed to confirm these findings, and to correlate viral load to clinical outcome.
B. Malette, None
B. Tapiero, None
V. Lamarre, None
F. Kakkar, None