Send to

Choose Destination
Clin Infect Dis. 2013 Jul;57(2):221-9. doi: 10.1093/cid/cit226. Epub 2013 Apr 10.

Evolution of treatment-emergent resistant variants in telaprevir phase 3 clinical trials.

Author information

Vertex Pharmaceuticals, Cambridge, MA 02139, USA.



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).


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.


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.


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.


DAA; clinical viral fitness; hepatitis C virus

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center