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No Evidence of Pritelivir Resistance Among Herpes Simplex Virus Type 2 Isolates After 4 Weeks of Daily Therapy.
- Source :
- Journal of Infectious Diseases; 7/15/2016, Vol. 214 Issue 2, p258-264, 7p
- Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>Pritelivir is a novel helicase-primase inhibitor in clinical development for treatment of herpes simplex virus type 2 (HSV-2) infections. In preclinical work, resistance-mediating mutations were identified in the HSV-2 genome at 3 loci in the UL5 gene and 1 locus in UL52.<bold>Methods: </bold>To evaluate whether daily pritelivir treatment results in emergence of resistance-mediating mutations, we analyzed HSV-2 strains detected in genital swab specimens from trial participants who were randomly assigned to receive different dosages of pritelivir. We sequenced resistance regions from 87 participants' samples, the UL5 gene in 73 samples from 44 participants, and the UL52 gene in 71 samples from 43 participants.<bold>Results: </bold>We found no evidence that pritelivir induced known resistance-mediating mutations or for amino acid variation at other loci. In one participant's HSV-2 isolate, we found a previously unidentified mutation close to the putative resistance-mediating region in UL5 and subsequently determined in vitro susceptibility to pritelivir. We characterized mutations from 32 cultivated HSV-2 isolates previously found to be susceptible to pritelivir in vitro and identified several novel mutations that most likely reflect preexisting variation in circulating HSV-2.<bold>Conclusions: </bold>This study demonstrates evidence of retained susceptibility of HSV-2 to pritelivir in immunocompetent persons following daily therapy for up to 28 days. [ABSTRACT FROM AUTHOR]
- Subjects :
- HERPES simplex virus
HERPESVIRUSES
HUMAN herpesvirus 1
THERAPEUTICS
CLINICAL medicine
ANTIVIRAL agents
COMPARATIVE studies
DRUG resistance in microorganisms
HERPES genitalis
RESEARCH methodology
MEDICAL cooperation
GENETIC mutation
PROTEINS
PYRIDINE
RESEARCH
RESEARCH funding
THIAZOLES
EVALUATION research
RANDOMIZED controlled trials
SEQUENCE analysis
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 00221899
- Volume :
- 214
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Journal of Infectious Diseases
- Publication Type :
- Academic Journal
- Accession number :
- 116410246
- Full Text :
- https://doi.org/10.1093/infdis/jiw129