Key result
Telaprevir-resistant variants developed in 77% of patients failing treatment, but were subsequently lost in 60% of these patients over a median follow-up of 9.6 months.
Why the study?
What is the frequency and retention of telaprevir-resistant variants in patients with genotype 1 HCV who do not achieve sustained virologic response?
Observational (n=1,797)
What is the frequency and retention of telaprevir-resistant variants in patients with genotype 1 HCV who do not achieve sustained virologic response?
Telaprevir-resistant variants are common after treatment failure but tend to be replaced by wild-type virus over time, particularly rapidly in subtype 1b infections.
Answers are grounded in this paper and cite their sources.
May guide retreatment timing after telaprevir failure; leaves open resistance dynamics with modern DAAs in genotype 1 HCV.
BACKGROUND: Telaprevir (TVR), a hepatitis C virus (HCV) NS3/4A protease inhibitor, has been approved to treat genotype 1 HCV. To understand the clinical impact of TVR-resistant variants, we analyzed samples from patients in phase 3 clinical trials to determine the frequency and retention of TVR-resistant variants in patients who did not achieve sustained virologic response (SVR). METHODS: A total of 1797 patients were treated with TVR. Resistant variants (V36A/G/I/L/M, T54A/S, I132V [subtype 1a only], R155G/K/T/M, A156F/N/S/T/V, and D168N) were identified after treatment failure and at visits thereafter, by direct (population) sequencing of the NS3/4A region. Kaplan-Meier analysis was used to determine median time to loss of these variants. RESULTS: Resistant variants were observed in 77% (299/388) of patients who did not achieve SVR. Resistance occurred more commonly in subtype 1a (86%; 232/269) than subtype 1b infections (56%; 67/119). After treatment failure, 355 patients had at least 1 follow-up visit (median follow-up period: 9.6 months). Of patients with resistance at time of failure and at least 1 follow-up visit, 60% (153/254) lost resistance. Kaplan-Meier analysis, including all patients with any sequence data after treatment failure, indicated that median time to wild type was 10.6 months (95% confidence interval [CI], 9.47-12.20) in subtype 1a and 0.9 months (95% CI, 0.00-2.07) in subtype 1b infections. CONCLUSIONS: After failure to achieve SVR with TVR-based treatment, resistant variants are observed in most patients. However, presumably due to the lower fitness of those variants, they tend to be replaced with wild-type virus over time.
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Sullivan et al. (2013) conducted an observational in Genotype 1 Hepatitis C virus (HCV) (n=1,797). Telaprevir was evaluated on Frequency of resistant variants in patients who did not achieve sustained virologic response. Telaprevir-resistant variants developed in 77% of patients failing treatment, but were subsequently lost in 60% of these patients over a median follow-up of 9.6 months.
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