Blood Viral Load in Symptomatic Congenital Cytomegalovirus Infection

• Published in: The Journal of infectious diseases Vol. 219; no. 9; pp. 1398 - 1406
• Main Authors: Marsico, Concetta, Aban, Immaculada, Kuo, Huichien, James, Scott H., Sanchez, Pablo J., Ahmed, Amina, Arav-Boger, Ravit, Michaels, Marian G., Ashouri, Negar, Englund, Janet A., Estrada, Benjamin, Jacobs, Richard F., Romero, José R., Sood, Sunil K., Whitworth, Suzanne, Jester, Penelope M., Whitley, Richard J., Kimberlin, David W.
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.05.2019
• Subjects: Administration, Intravenous; Administration, Oral; Antiviral agents; Antiviral Agents - administration & dosage; Antiviral Agents - therapeutic use; Antiviral drugs; Blood; Breakpoints; Central nervous system; Central Nervous System Diseases - virology; Child Development; Congenital diseases; Cytomegalovirus; Cytomegalovirus - genetics; Cytomegalovirus Infections - blood; Cytomegalovirus Infections - complications; Cytomegalovirus Infections - congenital; Cytomegalovirus Infections - drug therapy; DNA, Viral - blood; Female; Ganciclovir - therapeutic use; Hearing; Hearing loss; Hearing Loss - virology; Humans; Infant; Infant, Newborn; Infants; Major and Brief Reports; Male; Medical treatment; Polymerase chain reaction; Predictive Value of Tests; Sustained Virologic Response; Thrombocytopenia; Thrombocytopenia - virology; Valganciclovir - therapeutic use; Viral Load - drug effects; VIRUSES; viral load; hearing loss; congenital CMV infection; antiviral therapy
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiy695

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. In symptomatic congenital CMV infection, higher blood viral load before therapy correlates with thrombocytopenia, transaminitis, and CNS involvement but has little predictive value for long-term outcome. Early and sustained viral suppression during therapy may correlate with a better hearing outcome.