Details

Autor(en) / Beteiligte

• Svarovskaia, Evguenia S.
• Gane, Edward
• Dvory-Sobol, Hadas
• Martin, Ross
• Doehle, Brian
• Hedskog, Charlotte
• Jacobson, Ira M.
• Nelson, David R.
• Lawitz, Eric
• Brainard, Diana M.
• McHutchison, John G.
• Miller, Michael D.
• Mo, Hongmei

Titel

L159F and V321A Sofosbuvir-Associated Hepatitis C Virus NS5B Substitutions

Ist Teil von

• The Journal of infectious diseases, 2016-04, Vol.213 (8), p.1240-1247

Ort / Verlag

United States: Oxford University Press

Erscheinungsjahr

2016

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Background. Sofosbuvir (SOF) exhibits a high barrier to resistance, with no S282T NS5B substitution or phenotypic resistance detected in phase 3 registration studies. Methods. Here, emergence of the NS5B variants L159F and V321A and possible association with resistance was evaluated in 8 studies of SOF (NEUTRINO, FISSION, POSITRON, FUSION, VALENCE, PHOTON-1, PHOTON-2, and P7977-2025) and 5 studies of combination ledipasvir (LDV) and SOF (LDV/SOF; LONESTAR, ELECTRON [LDV/SOF arms], ION1, ION2, and ION3), using deep sequencing. Results. Deep sequencing detected L159F in 15% (53 of 353) and V321A in 5% (17 of 353) of patients with virologic failure in the SOF studies. Intensification of SOF treatment with LDV reduced the emergence of L159F or V321A to 2% (1 of 50 each) at virologic failure. L159F and V321A did not influence the outcome of retreatment with SOF, ribavirin, and pegylated interferon. At baseline, L159F was detected only in genotype 1-infected patients (1%) and was only associated with increased virologic failure in patients treated for short durations with SOF and ribavirin. Conclusions. Deep-sequencing analysis confirmed that NS5B variants L159F and V321A emerged in a subset of patients treated with SOF at virologic failure. These variants had no impact on retreatment outcome with SOF, ribavirin, and pegylated interferon. Baseline L159F in genotype 1 did not affect the treatment outcome with LDV/SOF.