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.
J Infect Dis
; 218(11): 1691-1699, 2018 10 20.
Article
em En
| MEDLINE
| ID: mdl-30020484
ABSTRACT
Background:
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.Methods:
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.Results:
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.Conclusion:
HSV genital shedding measured by PCR analysis in swab specimens self-collected daily is an appropriate surrogate outcome for genital herpes lesions because it is in the causal pathway to recurrences.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Herpes Genital
/
Eliminação de Partículas Virais
País/Região como assunto:
America do norte
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article