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Interferon ?-induced protein 10 kinetics in treatment-naive versus treatment-experienced patients receiving interferon-free therapy for hepatitis C virus infection: implications for the innate immune response.

ABSTRACT: We measured interferon ?-induced protein 10 (IP-10) levels in 428 patients at baseline, week 1, and week 2 of all-oral treatment for hepatitis C virus (HCV) infection. An increased baseline IP-10 level was associated with a T allele in the IL28B gene, an increased alanine aminotransferase level in treatment-naive but not experienced patients, and an increased body mass index. At week 1, the mean decline in plasma IP-10 levels was the same in treatment-naive and treatment-experienced patients (-49%), whereas during week 2 the mean decline in IP-10 levels in treatment-naive patients (-14%) was significantly larger than in treatment-experienced patients (-2%; P = .0176). IP-10 thus may be a surrogate marker of the rate of intracellular viral replication complex decay.

SUBMITTER: Lin JC

PROVIDER: S-EPMC4296177 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Interferon γ-induced protein 10 kinetics in treatment-naive versus treatment-experienced patients receiving interferon-free therapy for hepatitis C virus infection: implications for the innate immune response.

Lin Jennifer C JC Habersetzer François F Rodriguez-Torres Maribel M Afdhal Nezam N Lawitz Eric J EJ Paulson Matthew S MS Zhu Yanni Y Subramanian Gangadharan Mani GM McHutchison John G JG Sulkowski Mark M Wyles David L DL Schooley Robert T RT

The Journal of infectious diseases 20140606 12

We measured interferon γ-induced protein 10 (IP-10) levels in 428 patients at baseline, week 1, and week 2 of all-oral treatment for hepatitis C virus (HCV) infection. An increased baseline IP-10 level was associated with a T allele in the IL28B gene, an increased alanine aminotransferase level in treatment-naive but not experienced patients, and an increased body mass index. At week 1, the mean decline in plasma IP-10 levels was the same in treatment-naive and treatment-experienced patients (-4 ...[more]

PMID: 24907384

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Project description:BACKGROUND:In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR. METHODS:Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment. RESULTS:Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients. CONCLUSIONS:A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment.

Dataset Information

Interferon ?-induced protein 10 kinetics in treatment-naive versus treatment-experienced patients receiving interferon-free therapy for hepatitis C virus infection: implications for the innate immune response.

Publications

Interferon γ-induced protein 10 kinetics in treatment-naive versus treatment-experienced patients receiving interferon-free therapy for hepatitis C virus infection: implications for the innate immune response.

Similar Datasets

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