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.

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.

• Authors: Elfriede Agyemang, Amalia S Magaret, Stacy Selke, Christine Johnston, Larry Corey, Anna Wald
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 218 Issue 11 Pg. 1691-1699 (10 20 2018) ISSN: 1537-6613 [Electronic] United States
• PMID: 30020484 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antiviral Agents
• DNA, Viral

Topics

• Adult
• Aged
• Antiviral Agents (pharmacology, therapeutic use)
• Clinical Trials, Phase II as Topic
• Cohort Studies
• DNA, Viral (analysis, blood)
• Female
• Genitalia (pathology, virology)
• Herpes Genitalis (drug therapy, epidemiology, pathology, virology)
• Humans
• Male
• Middle Aged
• Randomized Controlled Trials as Topic
• Recurrence
• Treatment Outcome
• Virus Shedding (drug effects)
• Washington
• Young Adult