BACKGROUND: We investigated the frequency of RAVs among patients failing to achieve SVR in two clinical trials. We also investigated the impact of interferon responsiveness on RAVs and specific baseline RAVs relationship with boceprevir treatment failure. METHODS: Data are from 1020 patients enrolled into either SPRINT-2 or RESPOND-2; patients received a 4-week PR lead-in prior to receiving boceprevir or placebo. RAVs were analyzed via population-based sequence analysis of the NS3 protease gene (success rate of >90% at a virus level of ≥ 10,000IU/mL) RESULTS: The high SVR rate in patients who received boceprevir resulted in a low rate of RAVs; 7% was detected at baseline in all patients, which rose to 15% after treatment. However, RAVs were detected in 53% of patients that failed to achieve SVR, which declined to 22.8% 6-14 months following cessation of boceprevir therapy. Baseline RAVs alone were not predictive of virologic outcome; poor interferon responsiveness was highly predictive of non-SVR. RAVs were more frequently detected in poor interferon responders. CONCLUSIONS: We detected no association between the presence of baseline amino acid variants at boceprevir resistance-associated loci and outcome in the context of good IFN response.
BACKGROUND: We investigated the frequency of RAVs among patients failing to achieve SVR in two clinical trials. We also investigated the impact of interferon responsiveness on RAVs and specific baseline RAVs relationship with boceprevir treatment failure. METHODS: Data are from 1020 patients enrolled into either SPRINT-2 or RESPOND-2; patients received a 4-week PR lead-in prior to receiving boceprevir or placebo. RAVs were analyzed via population-based sequence analysis of the NS3 protease gene (success rate of >90% at a virus level of ≥ 10,000IU/mL) RESULTS: The high SVR rate in patients who received boceprevir resulted in a low rate of RAVs; 7% was detected at baseline in all patients, which rose to 15% after treatment. However, RAVs were detected in 53% of patients that failed to achieve SVR, which declined to 22.8% 6-14 months following cessation of boceprevir therapy. Baseline RAVs alone were not predictive of virologic outcome; poor interferon responsiveness was highly predictive of non-SVR. RAVs were more frequently detected in poor interferon responders. CONCLUSIONS: We detected no association between the presence of baseline amino acid variants at boceprevir resistance-associated loci and outcome in the context of good IFN response.
Authors: C K S Chui; W W Y Dong; J B Joy; A F Y Poon; W Y Dong; T Mo; C K Woods; C Beatty; H Hew; P R Harrigan; C J Brumme Journal: J Clin Microbiol Date: 2015-07-01 Impact factor: 5.948
Authors: Sonia Amelia Lozano-Sepulveda; Eduardo Bautista-Osorio; Jose Angel Merino-Mascorro; Marta Varela-Rey; Linda Elsa Muñoz-Espinosa; Paula Cordero-Perez; María Luz Martinez-Chantar; Ana Maria Rivas-Estilla Journal: World J Gastroenterol Date: 2016-04-14 Impact factor: 5.742
Authors: Rong Liu; Stephanie Curry; Patricia McMonagle; Wendy W Yeh; Steven W Ludmerer; Patricia A Jumes; William L Marshall; Stephanie Kong; Paul Ingravallo; Stuart Black; Irene Pak; Mark J DiNubile; Anita Y M Howe Journal: Antimicrob Agents Chemother Date: 2015-08-24 Impact factor: 5.938