Establishment of intracellular tenofovir-diphosphate as the key determinant for in vitro-in vivo translation of antiviral efficacy

• Published in: Antiviral research 2018-03, Vol.151, p.1-3
• Main Authors: Ma, Bennett, Barth, Aline, McHale, Carolyn M., Lai, Ming-Tain
• Format: Article
• Language: English
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2018.01.005

In vitro evaluation of tenofovir disproxil fumarate (TDF) and tenofovir alafenamide (TAF) revealed comparable antiviral effects with respect to the tenofovir-diphosphate (TFV-DP) level in human peripheral blood mononuclear cells (PBMCs), despite the EC50 values determined based on prodrug concentrations were nearly two orders of magnitude apart. In vivo EC50 obtained from meta-analyses were in good agreement with the in vitro results, indicating intracellular TFV-DP can be employed for in vitro-in vivo translation of viral inhibition for tenofovir prodrugs. Current analysis indicated that the intracellular concentrations of TFV-DP achieving maximal antiviral effect in vitro can be directly translatable in the clinic to accomplish maximal viral load suppression attainable by tenofovir-prodrugs. •In vitro EC50 values determined based on tenofovir-diphosphate (TFV-DP) were comparable for tenofovir prodrugs TDF and TAF.•In vivo EC50 obtained from meta-analyses were in good agreement with the in vitro results.•Intracellular TFV-DP can be employed for in vitro-in vivo translation of viral inhibition for tenofovir prodrugs.