Virologic breakthrough was often transient and usually associated with nonadherence to study medication with subsequent resuppression of HBV DNA <400 copies/mL. There was no accumulation of conserved site changes and no evidence of TDF resistance. These results support the long-term use of TDF for CHB treatment. Disclosures: Amoreena C. Corsa - Employment: Gilead Sciences Inc.; Stock Shareholder: Gilead Sciences Inc. Yang Liu - Employment: Gilead Sciences John F. Flaherty - Employment: Gilead Sciences Inc.; Stock Shareholder: Gilead Sciences Inc. Patrick Marcellin - Consulting: Roche, Gilead, BMS, Vertex, Novartis, Janssen, MSD, Abbvie, Alios BioPharma, Idenix, Akron; Grant/Research
Support: Roche, Gilead, BMS, Novartis, Janssen, MSD, Alios https://www.selleckchem.com/products/sch772984.html BioPharma; Speaking and Teaching: Roche, Gilead, BMS, Vertex, Novartis, Janssen, MSD, Boehringer, Pfizer, Abbvie Michael D. Miller – Employment: Gilead Sciences, Inc.; Stock Shareholder: Gil-ead Sciences, Inc. Kathryn M. Kitrinos – Employment: Gilead Sciences, Gilead Sciences; Stock Shareholder: Gilead Sciences, Gilead Sciences INTRODUCTION: Treatment strategies in Chronic Hepatitis B (CHB) are now focused on achieving HBsAg loss; therefore greater consideration is being given to combined/sequential Alvelestat manufacturer therapeutic approaches comprising Pegylated-Interferon (PEG-IFN-α) and nucleot(s)ide analogue (NUC) therapy, to achieve this goal. We
previously demonstrated boosting of NK cell responses in eAg- patients treated with PEG-IFN-α (Micco et al, J. Hepatol, 2013), and postulated that this effect could be maintained with sequential NUC therapy, representing a superior strategy to NUC monotherapy. Differential NK cell responses in patients receiving a sequential NUC were compared to patients on NUC monotherapy to determine if there was
a treatment advantage with PEG-IFN-α exposure. PATIENTS & METHODS: PBMC from 18 eAg+ patients during PEG-IFN-α therapy were utlised. 10/18 patients considered PEG-IFN-α non-responders after 48 weeks therapy progressed to sequential NUC therapy and were followed until virally suppressed. NUC monother-apy patients, without prior PEG-IFN-α exposure, were analysed Bcl-w for comparison. Phenotypic and functional analysis of NK cell subsets was performed by multicolour flow-cytometry. RESULTS: PEG-IFN-α expanded CD56bright NK cells by 3-fold (p=0.0001); this was maintained on sequential therapy but not seen with NUCs alone (p=0.03). NK cell expression of C-Type lectin and natural cytotoxicity receptors was analysed. All receptors, except NKG2D, were expressed at significantly higher levels on sequential NUCs vs. NUC monotherapy (p=<0.05), with marked augmentation in the expression of NKp30 and NKp46 on CD56bright NK cells (p=0.0001 & 0.002 respectively). The proportion of CD56bright NK cells expressing TRAIL was 3-fold higher on sequential NUC therapy compared with NUC monotherapy (p=0.007).