Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection

Results of an international, multicenter, double-blind, randomized clinical trial

Kenneth Fife, Rick A. Barbarash, Timothy Rudolph, Barry Degregorio, Robert Roth, W. B. Cameron, S. Stevens, S. Tyring, M. Lappin, C. Yockey, M. Hanson, B. Long, F. Snyder, S. Raffanti, M. Nelson, N. Tipton, T. Britton, R. Collins, E. Gontero, J. Geil & 38 others B. Wright, K. David-Bajar, H. Handsfield, S. Griffith, R. Davis, J. Lalonde, L. Wright, C. McCracken, R. Waddell, R. Patel, G. Minns, C. Briefer, D. Child, J. Kelsey, P. Woolley, R. Snow, S. Garland, E. Curless, S. Garland, E. Curless, S. Thatcher, M. Guill, D. Havlichek, B. Goh, G. Luzzi, P. Wood, L. Reza, C. Stabler, D. Katz, D. Grant, J. Campbell, T. Sedlacek, D. Van Amerongen, D. Cheetham, J. Wesp, J. Bingham, L. Dix, R. J. Crooks

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Background and Objectives: Valaciclovir, the L-valine ester prodrug of acyclovir, is much better absorbed than acyclovir and produces acyclovir exposures three to five times those attainable with the parent drug. Goals: To determine whether the improved bioavailability of valaciclovir and a more convenient, less frequent dose regimen can maintain the clinical efficacy previously demonstrated for acyclovir. Study Design: This was an international, multicenter, randomized, double-blind clinical trial comparing 10-day regimens of valaciclovir (1000 mg, twice daily) and acyclovir (200 mg, 5 times daily) in the treatment of 643 otherwise healthy adults (≤18 years of age) with first-episode genital herpes. Patients were evaluated clinically and lesions were staged and cultured on days 1, 2, 3, 5, 7, 10, 14, and then twice weekly until healed. Blood for herpes serology tests was obtained on days 1 and 14; hematology and chemistry toxicity screening was done on days 1 and 7. Results: Valaciclovir and acyclovir did not differ significantly in efficacy with respect to duration of viral shedding (hazard ratio, 1.00; 95% confidence interval [CI], 0.84-1.18), time to healing (hazard ratio, 1.08; 95% CI, 0.92-1.27), duration of pain (hazard ratio, 1.0; 95% CI, 0.85-1.18), and time to loss of all symptoms (hazard ratio, 1.02; 95% CI, 0.85-1.22). Patients with primary genital herpes (no preexisting antibody to either herpes simplex virus type at enrollment with seroconversion at day 14) had longer times to healing and longer duration of viral shedding and pain than patients with nonprimary first genital episodes. Adverse experiences were generally infrequent and mild and were comparable in the two treatment groups.

Original languageEnglish
Pages (from-to)481-486
Number of pages6
JournalSexually Transmitted Diseases
Volume24
Issue number8
DOIs
StatePublished - Sep 1997

Fingerprint

valacyclovir
Herpes Genitalis
Acyclovir
Randomized Controlled Trials
Infection
Confidence Intervals
Virus Shedding
Therapeutics
Pain
Prodrugs
Valine
Hematology
Simplexvirus
Serology
Biological Availability
Esters
Parents
Clinical Trials

ASJC Scopus subject areas

  • Dermatology
  • Public Health, Environmental and Occupational Health
  • Microbiology (medical)

Cite this

Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection : Results of an international, multicenter, double-blind, randomized clinical trial. / Fife, Kenneth; Barbarash, Rick A.; Rudolph, Timothy; Degregorio, Barry; Roth, Robert; Cameron, W. B.; Stevens, S.; Tyring, S.; Lappin, M.; Yockey, C.; Hanson, M.; Long, B.; Snyder, F.; Raffanti, S.; Nelson, M.; Tipton, N.; Britton, T.; Collins, R.; Gontero, E.; Geil, J.; Wright, B.; David-Bajar, K.; Handsfield, H.; Griffith, S.; Davis, R.; Lalonde, J.; Wright, L.; McCracken, C.; Waddell, R.; Patel, R.; Minns, G.; Briefer, C.; Child, D.; Kelsey, J.; Woolley, P.; Snow, R.; Garland, S.; Curless, E.; Garland, S.; Curless, E.; Thatcher, S.; Guill, M.; Havlichek, D.; Goh, B.; Luzzi, G.; Wood, P.; Reza, L.; Stabler, C.; Katz, D.; Grant, D.; Campbell, J.; Sedlacek, T.; Van Amerongen, D.; Cheetham, D.; Wesp, J.; Bingham, J.; Dix, L.; Crooks, R. J.

In: Sexually Transmitted Diseases, Vol. 24, No. 8, 09.1997, p. 481-486.

Research output: Contribution to journalArticle

Fife, K, Barbarash, RA, Rudolph, T, Degregorio, B, Roth, R, Cameron, WB, Stevens, S, Tyring, S, Lappin, M, Yockey, C, Hanson, M, Long, B, Snyder, F, Raffanti, S, Nelson, M, Tipton, N, Britton, T, Collins, R, Gontero, E, Geil, J, Wright, B, David-Bajar, K, Handsfield, H, Griffith, S, Davis, R, Lalonde, J, Wright, L, McCracken, C, Waddell, R, Patel, R, Minns, G, Briefer, C, Child, D, Kelsey, J, Woolley, P, Snow, R, Garland, S, Curless, E, Garland, S, Curless, E, Thatcher, S, Guill, M, Havlichek, D, Goh, B, Luzzi, G, Wood, P, Reza, L, Stabler, C, Katz, D, Grant, D, Campbell, J, Sedlacek, T, Van Amerongen, D, Cheetham, D, Wesp, J, Bingham, J, Dix, L & Crooks, RJ 1997, 'Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection: Results of an international, multicenter, double-blind, randomized clinical trial', Sexually Transmitted Diseases, vol. 24, no. 8, pp. 481-486. https://doi.org/10.1097/00007435-199709000-00007
Fife, Kenneth ; Barbarash, Rick A. ; Rudolph, Timothy ; Degregorio, Barry ; Roth, Robert ; Cameron, W. B. ; Stevens, S. ; Tyring, S. ; Lappin, M. ; Yockey, C. ; Hanson, M. ; Long, B. ; Snyder, F. ; Raffanti, S. ; Nelson, M. ; Tipton, N. ; Britton, T. ; Collins, R. ; Gontero, E. ; Geil, J. ; Wright, B. ; David-Bajar, K. ; Handsfield, H. ; Griffith, S. ; Davis, R. ; Lalonde, J. ; Wright, L. ; McCracken, C. ; Waddell, R. ; Patel, R. ; Minns, G. ; Briefer, C. ; Child, D. ; Kelsey, J. ; Woolley, P. ; Snow, R. ; Garland, S. ; Curless, E. ; Garland, S. ; Curless, E. ; Thatcher, S. ; Guill, M. ; Havlichek, D. ; Goh, B. ; Luzzi, G. ; Wood, P. ; Reza, L. ; Stabler, C. ; Katz, D. ; Grant, D. ; Campbell, J. ; Sedlacek, T. ; Van Amerongen, D. ; Cheetham, D. ; Wesp, J. ; Bingham, J. ; Dix, L. ; Crooks, R. J. / Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection : Results of an international, multicenter, double-blind, randomized clinical trial. In: Sexually Transmitted Diseases. 1997 ; Vol. 24, No. 8. pp. 481-486.
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abstract = "Background and Objectives: Valaciclovir, the L-valine ester prodrug of acyclovir, is much better absorbed than acyclovir and produces acyclovir exposures three to five times those attainable with the parent drug. Goals: To determine whether the improved bioavailability of valaciclovir and a more convenient, less frequent dose regimen can maintain the clinical efficacy previously demonstrated for acyclovir. Study Design: This was an international, multicenter, randomized, double-blind clinical trial comparing 10-day regimens of valaciclovir (1000 mg, twice daily) and acyclovir (200 mg, 5 times daily) in the treatment of 643 otherwise healthy adults (≤18 years of age) with first-episode genital herpes. Patients were evaluated clinically and lesions were staged and cultured on days 1, 2, 3, 5, 7, 10, 14, and then twice weekly until healed. Blood for herpes serology tests was obtained on days 1 and 14; hematology and chemistry toxicity screening was done on days 1 and 7. Results: Valaciclovir and acyclovir did not differ significantly in efficacy with respect to duration of viral shedding (hazard ratio, 1.00; 95{\%} confidence interval [CI], 0.84-1.18), time to healing (hazard ratio, 1.08; 95{\%} CI, 0.92-1.27), duration of pain (hazard ratio, 1.0; 95{\%} CI, 0.85-1.18), and time to loss of all symptoms (hazard ratio, 1.02; 95{\%} CI, 0.85-1.22). Patients with primary genital herpes (no preexisting antibody to either herpes simplex virus type at enrollment with seroconversion at day 14) had longer times to healing and longer duration of viral shedding and pain than patients with nonprimary first genital episodes. Adverse experiences were generally infrequent and mild and were comparable in the two treatment groups.",
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TY - JOUR

T1 - Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection

T2 - Results of an international, multicenter, double-blind, randomized clinical trial

AU - Fife, Kenneth

AU - Barbarash, Rick A.

AU - Rudolph, Timothy

AU - Degregorio, Barry

AU - Roth, Robert

AU - Cameron, W. B.

AU - Stevens, S.

AU - Tyring, S.

AU - Lappin, M.

AU - Yockey, C.

AU - Hanson, M.

AU - Long, B.

AU - Snyder, F.

AU - Raffanti, S.

AU - Nelson, M.

AU - Tipton, N.

AU - Britton, T.

AU - Collins, R.

AU - Gontero, E.

AU - Geil, J.

AU - Wright, B.

AU - David-Bajar, K.

AU - Handsfield, H.

AU - Griffith, S.

AU - Davis, R.

AU - Lalonde, J.

AU - Wright, L.

AU - McCracken, C.

AU - Waddell, R.

AU - Patel, R.

AU - Minns, G.

AU - Briefer, C.

AU - Child, D.

AU - Kelsey, J.

AU - Woolley, P.

AU - Snow, R.

AU - Garland, S.

AU - Curless, E.

AU - Garland, S.

AU - Curless, E.

AU - Thatcher, S.

AU - Guill, M.

AU - Havlichek, D.

AU - Goh, B.

AU - Luzzi, G.

AU - Wood, P.

AU - Reza, L.

AU - Stabler, C.

AU - Katz, D.

AU - Grant, D.

AU - Campbell, J.

AU - Sedlacek, T.

AU - Van Amerongen, D.

AU - Cheetham, D.

AU - Wesp, J.

AU - Bingham, J.

AU - Dix, L.

AU - Crooks, R. J.

PY - 1997/9

Y1 - 1997/9

N2 - Background and Objectives: Valaciclovir, the L-valine ester prodrug of acyclovir, is much better absorbed than acyclovir and produces acyclovir exposures three to five times those attainable with the parent drug. Goals: To determine whether the improved bioavailability of valaciclovir and a more convenient, less frequent dose regimen can maintain the clinical efficacy previously demonstrated for acyclovir. Study Design: This was an international, multicenter, randomized, double-blind clinical trial comparing 10-day regimens of valaciclovir (1000 mg, twice daily) and acyclovir (200 mg, 5 times daily) in the treatment of 643 otherwise healthy adults (≤18 years of age) with first-episode genital herpes. Patients were evaluated clinically and lesions were staged and cultured on days 1, 2, 3, 5, 7, 10, 14, and then twice weekly until healed. Blood for herpes serology tests was obtained on days 1 and 14; hematology and chemistry toxicity screening was done on days 1 and 7. Results: Valaciclovir and acyclovir did not differ significantly in efficacy with respect to duration of viral shedding (hazard ratio, 1.00; 95% confidence interval [CI], 0.84-1.18), time to healing (hazard ratio, 1.08; 95% CI, 0.92-1.27), duration of pain (hazard ratio, 1.0; 95% CI, 0.85-1.18), and time to loss of all symptoms (hazard ratio, 1.02; 95% CI, 0.85-1.22). Patients with primary genital herpes (no preexisting antibody to either herpes simplex virus type at enrollment with seroconversion at day 14) had longer times to healing and longer duration of viral shedding and pain than patients with nonprimary first genital episodes. Adverse experiences were generally infrequent and mild and were comparable in the two treatment groups.

AB - Background and Objectives: Valaciclovir, the L-valine ester prodrug of acyclovir, is much better absorbed than acyclovir and produces acyclovir exposures three to five times those attainable with the parent drug. Goals: To determine whether the improved bioavailability of valaciclovir and a more convenient, less frequent dose regimen can maintain the clinical efficacy previously demonstrated for acyclovir. Study Design: This was an international, multicenter, randomized, double-blind clinical trial comparing 10-day regimens of valaciclovir (1000 mg, twice daily) and acyclovir (200 mg, 5 times daily) in the treatment of 643 otherwise healthy adults (≤18 years of age) with first-episode genital herpes. Patients were evaluated clinically and lesions were staged and cultured on days 1, 2, 3, 5, 7, 10, 14, and then twice weekly until healed. Blood for herpes serology tests was obtained on days 1 and 14; hematology and chemistry toxicity screening was done on days 1 and 7. Results: Valaciclovir and acyclovir did not differ significantly in efficacy with respect to duration of viral shedding (hazard ratio, 1.00; 95% confidence interval [CI], 0.84-1.18), time to healing (hazard ratio, 1.08; 95% CI, 0.92-1.27), duration of pain (hazard ratio, 1.0; 95% CI, 0.85-1.18), and time to loss of all symptoms (hazard ratio, 1.02; 95% CI, 0.85-1.22). Patients with primary genital herpes (no preexisting antibody to either herpes simplex virus type at enrollment with seroconversion at day 14) had longer times to healing and longer duration of viral shedding and pain than patients with nonprimary first genital episodes. Adverse experiences were generally infrequent and mild and were comparable in the two treatment groups.

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