Herpes Simplex Virus Shedding Rate: Surrogate Outcome for Genital Herpes Recurrence Frequency and Lesion Rates, and Phase 2 Clinical Trials End Point for Evaluating Efficacy of Antivirals

The Journal of Infectious Diseases
Elfriede AgyemangA Wald

Abstract

We tested whether genital herpes simplex virus (HSV) shedding is an appropriate surrogate outcome for the clinical outcome of genital herpes lesions in studies of HSV-2 antiviral interventions. We analyzed prospective data from natural history studies and clinical trials of antiviral agents for HSV-2 in which HSV-2-seropositive participants provided self-collected anogenital swab specimens daily over ≥25 days for HSV DNA quantitation by polymerase chain reaction (PCR). Genital recurrences were self-reported. Among 674 participants, genital HSV shedding was detected on 17% of days, and genital lesions were reported on 10% of days. Within the same session, HSV shedding rates were strongly correlated with lesion rates (ρ = 0.61, P < .0001). The relative reduction in the recurrence rate was 72% (P = .041) for recipients of the antiviral agent pritelivir as compared to recipients of placebo, but it decreased to 21% (P = .75) after adjustment for HSV shedding rate. When evaluating valacyclovir and acyclovir, adjustment for the HSV shedding rate also led to a reduced association of these antivirals with the recurrence rate. Overall, 40%-82% of the antiviral effect on recurrences was explained by its effect on HSV shedding. HSV genital...Continue Reading

References

Jan 30, 1992·Statistics in Medicine·L S FreedmanA Schatzkin
Jul 20, 1982·The American Journal of Medicine·L CoreyK K Holmes
Jul 20, 1982·The American Journal of Medicine·A P FiddianK Wikstrom
Jan 1, 1996·Annals of Internal Medicine·A WaldL Corey
Sep 21, 1995·The New England Journal of Medicine·A WaldL Corey
Oct 1, 1996·Annals of Internal Medicine·T R Fleming, D L DeMets
Jul 15, 1997·American Journal of Epidemiology·L S Magder, J P Hughes
Aug 27, 1999·JAMA : the Journal of the American Medical Association·R Temple
Jun 12, 2004·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·R Ashley-MorrowJ Smith
Jun 17, 2004·Statistical Methods in Medical Research·Geert MolenberghsMarc Buyse
Sep 21, 2004·The Journal of Infectious Diseases·Rachna GuptaLawrence Corey
Jan 14, 2005·Health Affairs·Thomas R Fleming
Aug 19, 2005·Nature·David G Bowen, Christopher M Walker
Oct 28, 2005·Statistics in Medicine·Christopher J Weir, Rosalind J Walley
Jun 3, 2006·The Journal of Infectious Diseases·Anna WaldJudy Zeh
Mar 3, 2007·Journal of Clinical Microbiology·Amalia S MagaretLarry Corey
Jun 6, 2009·The New England Journal of Medicine·Andreas H DiaconDavid F Mc Neeley
Feb 4, 2011·The Journal of Infectious Diseases·Warren PhippsAnna Wald
Apr 8, 2011·Science Translational Medicine·Jared M BaetenUNKNOWN Partners in Prevention HSV/HIV Transmission Study Team
Apr 14, 2011·JAMA : the Journal of the American Medical Association·Elizabeth TronsteinAnna Wald
Jun 20, 2012·Statistics in Medicine·Thomas R Fleming, John H Powers
Mar 27, 2013·JAMA Internal Medicine·Staffan SvenssonJoel Lexchin
Nov 22, 2013·The Annals of Pharmacotherapy·Elias B ChahineHanine Mansour
Jan 17, 2014·The New England Journal of Medicine·Anna WaldAlexander Birkmann
Mar 29, 2014·Journal of the Royal Society, Interface·Joshua T SchifferAnna Wald
May 2, 2014·Statistics in Medicine·Fumiaki Kobayashi, Manabu Kuroki
Oct 12, 2017·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Yoichiro NatoriUNKNOWN CMV Consensus Forum

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Citations

Jul 19, 2018·The Journal of Infectious Diseases·Kenneth H Fife
Jul 15, 2020·Open Forum Infectious Diseases·Joshua T SchifferLawrence Corey
Jul 28, 2020·The Journal of Infectious Diseases·Alpana WaghmareJoshua T Schiffer
Dec 8, 2021·Biometrics·Layla ParastLu Tian

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