No Evidence of Pritelivir Resistance Among Herpes Simplex Virus Type 2 Isolates After 4 Weeks of Daily Therapy.

Publication Type:

Journal Article

Source:

The Journal of infectious diseases, Volume 214, Issue 2, p.258-264 (2016)

Abstract:

BACKGROUND:  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 three loci in the UL5 gene and one locus in UL52. METHODS:  To evaluate whether daily pritelivir treatment results in emergence of resistance-mediating mutations, we analyzed HSV-2 strains detected in genital swabs from trial participants who were randomly assigned to different dosages of pritelivir. We sequenced resistance regions from 87 participants' samples, the UL5 gene in 73 samples from 44 participants, and UL52 in 71 samples from 43 participants. RESULTS:  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 determinedin vitrosensitivity to pritelivir. We characterized mutations from 32 cultivated HSV-2 isolates previously found to be sensitive to pritelivirin vitroand identified several novel mutations that most likely reflect pre-existing variation in circulating HSV-2. CONCLUSIONS:  This study demonstrates evidence of retained sensitivity of HSV-2 to pritelivir in immunocompetent persons following daily therapy up to 28 days.