Clinical evaluation of herPHEgen®: a herpesvirus genotype-to-phenotype antiviral resistance database and testing service
PHE ePoster Library. Mohamed H. Apr 9, 2019; 259604; 15570
Dr. Hodan Mohamed
Dr. Hodan Mohamed
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Abstract
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Abstract Herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) infections may be life-threatening in immunocompromised patients. Antiviral treatment is available but resistance can develop. The gold standard for resistance testing is cell culture-based phenotyping which is slow (3-4 weeks) and has a high (50%) failure rate. Faster genotypic testing (<10 working days) of viral thymidine kinase (TK) and DNA polymerase (DNApol) can be used with >95% success rate. However, a reference database for interpreting drug susceptibility from genetic data is lacking.We have developed an HSV genotypic test and genotype-to-phenotype drug resistance database. We evaluated the service using 325 clinical samples, previously characterised by phenotypic susceptibility testing, from 248 treatment-experienced patients. The median age was 42.5 years [30.0-51.0, IQR] and 50.8% (n=126) were female. Clinical details were as follows: 42.3% (n=105) haemato-oncology patients; 12.1% (n=30) HIV-infected; 4.4% (n=11) unspecified immunosuppression; 2.4% (n=6) congenital infection; 1.2% (n=3) solid organ transplant; 37.5% (n=93) unknown.HSV-1 was identified in 58.2% (n=189) samples. Phenotypic testing identified resistance in 63.7% (n=207) samples. Genotypic testing identified a resistance-associated mutation (RAM) in TK and/or DNApol in 200/207 samples, a positive percent agreement of 96.6%, whereas a RAM was detected in 1/118 susceptible samples, a negative percent agreement of 99.2%. Most RAM occurred in TK (n=195; 97.0%) with few in DNApol (n=32; 15.9%).In summary, through herPHEgen we have developed a robust HSV resistance testing service, providing clinicians with timely and accurate results. This will improve clinical decision-making, optimising treatment efficacy and minimising toxicity in immunocompromised patients with HSV. Funding PHE Pipeline funding
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