Blood Viral Load in Symptomatic Congenital Cytomegalovirus Infection

Abstract

Background: Viral loads (VLs) frequently are followed during treatment of symptomatic congenital cytomegalovirus disease, but their predictive value is unclear.

Methods: Post hoc analysis of 2 antiviral studies was performed. Seventy-three subjects were treated for 6 weeks and 47 subjects were treated for 6 months. Whole blood VL was determined by real-time polymerase chain reaction before and during therapy.

Results: Higher baseline VL was associated with central nervous system involvement (3.82 log, range 1-5.65 vs 3.32 log, range 1-5.36; P = .001), thrombocytopenia (3.68 log, range 1-5.65 vs 3.43 log, range 1-5.36; P = .03), and transaminitis at presentation (3.73 log, range 1-5.60 vs 3.39 log, range 1-5.65; P = .009), but with overlap in the amount of virus detected between groups. In subjects treated for 6 months, lower VL at presentation correlated with better hearing outcomes at 12 months, but VL breakpoints predictive of hearing loss were not identified. Sustained viral suppression during 6 months of therapy correlated with better hearing outcomes at 6, 12, and 24 months (P = .01, P = .0007, P = .04), but a majority without viral suppression still had improved hearing.

Conclusions: In infants with symptomatic congenital cytomegalovirus disease, higher whole blood VL before initiation of antiviral therapy has no clinically meaningful predictive value for long-term outcomes.

Keywords: antiviral therapy; congenital CMV infection; hearing loss; viral load.

Figure 1.

Correlation between baseline viral load in subjects with and without central nervous system (CNS) involvement (P = .0010), thrombocytopenia (P = .0307), elevated alanine aminotransferase (ALT), and/or aspartate aminotransferase ([AST]; P = .0087), analyzed by Wilcoxon two-samples test. IE, immediate early. Note: The box represents the middle 50% of the data; the line in the box represents the median value; the whiskers represent the ranges for the bottom 25% and the top 25% of the data values, excluding outliers.

Figure 2.

Viral load decline after 7 and 14 days of treatment in subjects receiving intravenous (iv) ganciclovir (GCV) and subjects receiving oral valganciclovir (VGCV). A general linear model for repeated measures was used to analyze the effect of drug, day, and their interaction on the viral load (treatment effect P = .67; day effect P < .001; interaction with treatment and day P = .0021). Note: The box represents the middle 50% of the data; the line in the box represents the median value; the whiskers represent the ranges for the bottom 25% and the top 25% of the data values, excluding outliers.