Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth

Results of a phase I/II trial

David Kimberlin, Dwight Powell, William Gruber, Pamela Diaz, Ann Arvin, Mary Kumar, Richard Jacobs, Russell Van Dyke, Sandra Burchett, Seng Jaw Soong, Alfred Lakeman, Richard Whitley, C. Laughlin, R. Whitley, A. Lakeman, S. J. Soong, D. Kimberlin, S. Stagno, R. Pass, A. Arvin & 38 others C. Prober, J. Bradley, S. Spector, L. Corey, G. Demmler, S. Burchett, S. Adler, J. Bale, Y. Bryson, T. Chonmaitree, P. Diaz, J. Gross, W. Gruber, R. Jacobs, H. Keyserling, J. Kinney, A. Kovacs, M. Kumar, S. Laudert, C. Leach, E. Leistikow, R. McKinney, C. Meissner, J. Modlin, D. Powell, M. Rathore, P. Reuman, J. Robinson, W. Vaudry, C. Sander, M. Shelton, M. De Sierra, L. Stanberry, S. Starr, R. Steele, G. Storch, R. Van Dyke, L. Weiner

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Background. Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. Methods. Infants ≤1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m 2/dose given either twice daily or three times per day) was administered for 6 months. Results. Twelve (46%) of the 26 infants developed neutropenia (<1000 cells/mm 3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study. Conclusions. Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.

Original languageEnglish (US)
Pages (from-to)247-254
Number of pages8
JournalPediatric Infectious Disease Journal
Volume15
Issue number3
DOIs
StatePublished - 1996

Fingerprint

Acyclovir
Virus Diseases
Simplexvirus
Oral Administration
Mouth
Mouth Diseases
Skin
Recurrence
Eye Diseases
Skin Diseases
Nervous System
Therapeutics
Antiviral Agents
Infant, Newborn, Diseases
National Institute of Allergy and Infectious Diseases (U.S.)
Human Herpesvirus 2
Neurologic Manifestations
Neonatal herpes
Neutropenia
Cerebrospinal Fluid

Keywords

  • acyclovir
  • herpes simplex
  • Newborn
  • prophylaxis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Microbiology (medical)

Cite this

Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth : Results of a phase I/II trial. / Kimberlin, David; Powell, Dwight; Gruber, William; Diaz, Pamela; Arvin, Ann; Kumar, Mary; Jacobs, Richard; Van Dyke, Russell; Burchett, Sandra; Soong, Seng Jaw; Lakeman, Alfred; Whitley, Richard; Laughlin, C.; Whitley, R.; Lakeman, A.; Soong, S. J.; Kimberlin, D.; Stagno, S.; Pass, R.; Arvin, A.; Prober, C.; Bradley, J.; Spector, S.; Corey, L.; Demmler, G.; Burchett, S.; Adler, S.; Bale, J.; Bryson, Y.; Chonmaitree, T.; Diaz, P.; Gross, J.; Gruber, W.; Jacobs, R.; Keyserling, H.; Kinney, J.; Kovacs, A.; Kumar, M.; Laudert, S.; Leach, C.; Leistikow, E.; McKinney, R.; Meissner, C.; Modlin, J.; Powell, D.; Rathore, M.; Reuman, P.; Robinson, J.; Vaudry, W.; Sander, C.; Shelton, M.; De Sierra, M.; Stanberry, L.; Starr, S.; Steele, R.; Storch, G.; Van Dyke, R.; Weiner, L.

In: Pediatric Infectious Disease Journal, Vol. 15, No. 3, 1996, p. 247-254.

Research output: Contribution to journalArticle

Kimberlin, D, Powell, D, Gruber, W, Diaz, P, Arvin, A, Kumar, M, Jacobs, R, Van Dyke, R, Burchett, S, Soong, SJ, Lakeman, A, Whitley, R, Laughlin, C, Whitley, R, Lakeman, A, Soong, SJ, Kimberlin, D, Stagno, S, Pass, R, Arvin, A, Prober, C, Bradley, J, Spector, S, Corey, L, Demmler, G, Burchett, S, Adler, S, Bale, J, Bryson, Y, Chonmaitree, T, Diaz, P, Gross, J, Gruber, W, Jacobs, R, Keyserling, H, Kinney, J, Kovacs, A, Kumar, M, Laudert, S, Leach, C, Leistikow, E, McKinney, R, Meissner, C, Modlin, J, Powell, D, Rathore, M, Reuman, P, Robinson, J, Vaudry, W, Sander, C, Shelton, M, De Sierra, M, Stanberry, L, Starr, S, Steele, R, Storch, G, Van Dyke, R & Weiner, L 1996, 'Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: Results of a phase I/II trial', Pediatric Infectious Disease Journal, vol. 15, no. 3, pp. 247-254. https://doi.org/10.1097/00006454-199603000-00014
Kimberlin, David ; Powell, Dwight ; Gruber, William ; Diaz, Pamela ; Arvin, Ann ; Kumar, Mary ; Jacobs, Richard ; Van Dyke, Russell ; Burchett, Sandra ; Soong, Seng Jaw ; Lakeman, Alfred ; Whitley, Richard ; Laughlin, C. ; Whitley, R. ; Lakeman, A. ; Soong, S. J. ; Kimberlin, D. ; Stagno, S. ; Pass, R. ; Arvin, A. ; Prober, C. ; Bradley, J. ; Spector, S. ; Corey, L. ; Demmler, G. ; Burchett, S. ; Adler, S. ; Bale, J. ; Bryson, Y. ; Chonmaitree, T. ; Diaz, P. ; Gross, J. ; Gruber, W. ; Jacobs, R. ; Keyserling, H. ; Kinney, J. ; Kovacs, A. ; Kumar, M. ; Laudert, S. ; Leach, C. ; Leistikow, E. ; McKinney, R. ; Meissner, C. ; Modlin, J. ; Powell, D. ; Rathore, M. ; Reuman, P. ; Robinson, J. ; Vaudry, W. ; Sander, C. ; Shelton, M. ; De Sierra, M. ; Stanberry, L. ; Starr, S. ; Steele, R. ; Storch, G. ; Van Dyke, R. ; Weiner, L. / Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth : Results of a phase I/II trial. In: Pediatric Infectious Disease Journal. 1996 ; Vol. 15, No. 3. pp. 247-254.
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abstract = "Background. Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. Methods. Infants ≤1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m 2/dose given either twice daily or three times per day) was administered for 6 months. Results. Twelve (46{\%}) of the 26 infants developed neutropenia (<1000 cells/mm 3) while receiving acyclovir. Thirteen (81{\%}) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54{\%} of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study. Conclusions. Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.",
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TY - JOUR

T1 - Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth

T2 - Results of a phase I/II trial

AU - Kimberlin, David

AU - Powell, Dwight

AU - Gruber, William

AU - Diaz, Pamela

AU - Arvin, Ann

AU - Kumar, Mary

AU - Jacobs, Richard

AU - Van Dyke, Russell

AU - Burchett, Sandra

AU - Soong, Seng Jaw

AU - Lakeman, Alfred

AU - Whitley, Richard

AU - Laughlin, C.

AU - Whitley, R.

AU - Lakeman, A.

AU - Soong, S. J.

AU - Kimberlin, D.

AU - Stagno, S.

AU - Pass, R.

AU - Arvin, A.

AU - Prober, C.

AU - Bradley, J.

AU - Spector, S.

AU - Corey, L.

AU - Demmler, G.

AU - Burchett, S.

AU - Adler, S.

AU - Bale, J.

AU - Bryson, Y.

AU - Chonmaitree, T.

AU - Diaz, P.

AU - Gross, J.

AU - Gruber, W.

AU - Jacobs, R.

AU - Keyserling, H.

AU - Kinney, J.

AU - Kovacs, A.

AU - Kumar, M.

AU - Laudert, S.

AU - Leach, C.

AU - Leistikow, E.

AU - McKinney, R.

AU - Meissner, C.

AU - Modlin, J.

AU - Powell, D.

AU - Rathore, M.

AU - Reuman, P.

AU - Robinson, J.

AU - Vaudry, W.

AU - Sander, C.

AU - Shelton, M.

AU - De Sierra, M.

AU - Stanberry, L.

AU - Starr, S.

AU - Steele, R.

AU - Storch, G.

AU - Van Dyke, R.

AU - Weiner, L.

PY - 1996

Y1 - 1996

N2 - Background. Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. Methods. Infants ≤1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m 2/dose given either twice daily or three times per day) was administered for 6 months. Results. Twelve (46%) of the 26 infants developed neutropenia (<1000 cells/mm 3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study. Conclusions. Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.

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KW - Newborn

KW - prophylaxis

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