947. Blood Viral Load (VL) Not Clinically Meaningful in Symptomatic Congenital Cytomegalovirus (cCMV) Infection
Session: Oral Abstract Session: Emerging Paradigms: Pediatric Viral Infections
Friday, October 6, 2017: 9:15 AM
Room: 01AB

Background: Sensorineural hearing loss (SNHL) and neurodevelopmental (ND) outcomes are favorably impacted by antiviral therapy in infants with symptomatic cCMV disease. We correlated blood VL before and during therapy with clinical findings at presentation and follow-up in this population.

Methods: Post-hoc analysis of 2 clinical trials conducted by the CASG from 2002-2013 evaluating valganciclovir therapy. 120 subjects (73 treated x 6 weeks, 47 treated x 6 months) were included. Whole blood VL was determined by real-time PCR at a central laboratory before therapy (baseline, BL) and periodically for 6 months.

Results: In subjects treated for 6 months, increases in BL VL correlated with decreased probability of better hearing outcomes at 12 months (Figure 1), but clinically meaningful VL thresholds that predict SNHL were not identified (Table 1). Subjects treated for 6 weeks had no correlation between BL VL and SNHL. No correlation was found between BL VL and Bayley ND testing at 12 and 24 months for subjects receiving either treatment duration. Subjects treated for 6 months who achieved and sustained VL suppression (<2.5log) between treatment day 14 and month 4 had better hearing outcomes at 6, 12, and 24 months (89% vs. 56%, P=0.01; 100% vs. 63%, P=0.0007; 94% vs. 68%, P=0.04), but 56%-68% of subjects not achieving suppression still had improved hearing. Higher BL VL correlated with BL CNS involvement, thrombocytopenia, and transaminase elevation for subjects receiving either treatment duration, but with substantial overlap in quantity of virus detected (Figure 2). Subjects with >3 symptoms of congenital CMV at presentation had higher BL VL than subjects with ≤3 symptoms (3.75 log, range 1.00-5.65, vs. 3.38 log, range 1.00-5.36; P=0.005).

Conclusion: Blood VL at BL and during therapy has little clinically meaningful predictive value for long-term outcomes in symptomatic congenital CMV.

Table 1

BL VL

(log genome equivalent/mL)

Hearing outcome

P-value

Negative Predictive Value

(CI)

Positive Predictive Value

(CI)

Improved/protected (no.)

Others (no.)

 

12 months

 

 

 

> 3

43

20

0.10

93

(79-100)

32

(20-43)

≤ 3

13

1

> 4.5

8

9

0.01

80

(70-90)

53

(29-77)

≤ 4.5

48

12

 

24 months

 

 

 

> 3

42

14

0.72

83

(62-100)

25

(14-36)

≤ 3

10

2

> 4.5

10

5

0.32

79

(68-90)

33

(9-57)

≤ 4.5

42

11

 Figure 1

Figure 2

 

Concetta Marsico, MD1, Inmaculada Aban, PhD2, Huichien Kuo, MS2, Pablo J. Sanchez, MD, FIDSA, FPIDS3, Amina Ahmed, MD4, Ravit Arav-Boger, MD5, Marian Michaels, MD, MPH6, Negar Ashouri, MD7, Janet Englund, MD, FIDSA8, Benjamin Estrada, MD, FPIDS9, Richard Jacobs, MD, FIDSA, FPIDS10, Jose R. Romero, MD11, Sunil Sood, MD, FIDSA12, Suzanne Whitworth, MD13, Scott H. James, MD14, Penny Jester, RN2, Richard Whitley, MD, FIDSA14, David W. Kimberlin, MD, FIDSA, FPIDS15 and Collaborative Antiviral Study Group (CASG), (1)University of Bologna, Bologna, Italy, (2)University of Alabama at Birmingham, Birmingham, AL, (3)Pediatrics, Divisions of Pediatric Infectious Diseases and Neonatology, Nationwide Children's Hospital - Ohio State University College of Medicine, Columbus, OH, (4)Pediatrics, Carolinas Medical Center, Charlotte, NC, (5)Johns Hopkins, Baltimore, MD, (6)Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, (7)Infectious Diseases, CHOC Children's Hospital, Orange, CA, (8)University of Washington/Seattle Children's Hospital, Seattle, WA, (9)University of South Alabama, Mobile, AL, (10)University of Arkansas, Little Rock, AR, (11)University of Arkansas for Medical Sciences, Little Rock, AR, (12)Steven and Alexandra Cohen Children's Medical Center, New Hyde Park, NY, (13)Cook Children's Medical Center, Fort Worth, TX, (14)Pediatrics, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, (15)Pediatrics, University of Alabama at Birmingham, Birmingham, AL

Disclosures:

C. Marsico, None

I. Aban, None

H. Kuo, None

P. J. Sanchez, None

A. Ahmed, None

R. Arav-Boger, None

M. Michaels, None

N. Ashouri, None

J. Englund, Gilead: Consultant and Investigator , Research support
Chimerix: Investigator , Research support
Alios: Investigator , Research support
Novavax: Investigator , Research support
MedImmune: Investigator , Research support
GlaxoSmithKline: Investigator , Research support

B. Estrada, None

R. Jacobs, None

J. R. Romero, None

S. Sood, None

S. Whitworth, None

S. H. James, None

P. Jester, None

R. Whitley, None

D. W. Kimberlin, None

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