Resistance-associated amino acid variants associated with boceprevir plus pegylated interferon-α2b and ribavirin in patients with chronic hepatitis C in the SPRINT-1 trial.

Autor:	Ogert RA; Merck Sharp & Dohme Corporation, Whitehouse Station, NJ, USA. robert.ogert@merck.com, Howe JA, Vierling JM, Kwo PY, Lawitz EJ, McCone J, Schiff ER, Pound D, Davis MN, Gordon SC, Ravendhran N, Rossaro L, Jacobson IM, Ralston R, Chaudhri E, Qiu P, Pedicone LD, Brass CA, Albrecht JK, Barnard RJ, Hazuda DJ, Howe AY
Jazyk:	angličtina
Zdroj:	Antiviral therapy [Antivir Ther] 2013; Vol. 18 (3), pp. 387-97. Date of Electronic Publication: 2013 Feb 13.
DOI:	10.3851/IMP2549
Abstrakt:	Background: Resistance to direct-acting antivirals represents a new challenge in the treatment of chronic hepatitis C. Methods: SPRINT-1 was a randomized study of treatment-naive patients with genotype (G) 1 hepatitis C infection (n=595) that evaluated the safety and efficacy of boceprevir (BOC) when added to pegylated interferon-α2b plus ribavirin (PR). Plasma samples collected at protocol-specified visits were analysed by population sequencing for detection of BOC-associated resistance-associated variants (RAVs). Results: A total of 17/24 (71%) patients randomized to BOC with baseline RAVs achieved sustained virological response (SVR). V55A/I (n=14), Q41H (n=11) and T54S (n=9) were the most frequently detected polymorphisms at baseline. Seven non-SVR patients with baseline RAVs had V55A (relapse, n=3; breakthrough, n=1; and non-response, n=1) and/or R155K (non-response, n=2). In total, 63/144 (44%) patients with sequenced post-baseline samples (2 SVR, 61 non-SVR) had detectable RAVs after BOC treatment (G1a: R155K [39/49; 80%], V36M [37/49; 76%] and T54S [24/49; 49%]; G1b: T54S [3/11; 27%], T54A [4/11; 35%], A156S [2/11; 18%] and V170A [2/11; 18%]). RAV frequency varied according to the virological response: 90%, 67%, 27% and 37% of breakthrough, incomplete virological response, relapse and non-responder patients, respectively, had post-baseline RAVs present. Similar RAVs were identified in both the PR lead-in and no-lead-in arms and the frequency of post-baseline RAVs was highest in the low-dose ribavirin arm. Conclusions: SVR rates were not compromised among patients with RAVs at baseline; however, a lower starting mg/kg dose of ribavirin was associated with a higher frequency of post-baseline RAVs.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu