Week 96 resistance analyses of the once-daily, single-tablet regimen (STR) darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV-1 from the phase 3 randomized AMBER and EMERALD trials.

In AMBER and EMERALD, darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg demonstrated high virological response and low virological failure (VF) through week 96. Week 96 resistance analyses are presented. Post-baseline samples for genotyping/phenotyping were analyzed from protocol-defined-VFs with viral load (VL) ≥ 400 copies/ml at failure/later time points.

Week 48 Resistance Analyses of the Once-Daily, Single-Tablet Regimen Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Adults Living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) ≥400 copies/mL at failure/later time points.

Evolution of hepatitis C virus quasispecies during repeated treatment with the NS3/4A protease inhibitor telaprevir.

In treating hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections, the rapid reselection of resistance-associated variants (RAVs) is well known in patients with repeated exposure to the same class of antiviral agents. For chronic hepatitis C patients who have experienced virologic failure with direct-acting antiviral drugs, the potential for the reselection of persistent RAVs is unknown. Nine patients who received 14 days of telaprevir monotherapy were retreated with telaprevir-based triple therapy 4.

An OPTIMIZE study retrospective analysis for management of telaprevir-treated hepatitis C virus (HCV)-infected patients by use of the Abbott RealTime HCV RNA assay.

Protease inhibitor (PI)-based response-guided triple therapies for hepatitis C virus (HCV) infection are still widely used. Noncirrhotic treatment-naive and prior relapser patients receiving telaprevir-based treatment are eligible for shorter, 24-week total therapy if HCV RNA is undetectable at both weeks 4 and 12. In this study, the concordance in HCV RNA assessments between the Roche High Pure System/Cobas TaqMan and Abbott RealTime HCV RNA assays and the impacts of different HCV RNA cutoffs on treatment outcome were evaluated.

Prevalence of the hepatitis C virus NS3 polymorphism Q80K in genotype 1 patients in the European region.

Hepatitis C virus (HCV) NS3 polymorphism Q80K is mainly found in patients with HCV genotype (G) 1a, and has been associated with a reduced treatment response to simeprevir with pegylated interferon (P) and ribavirin (R). Prevalence of Q80K among G1 patients may vary geographically. Q80K prevalence in the North-American G1 population in a recent study was 34%.

Modeling viral evolutionary dynamics after telaprevir-based treatment.

For patients infected with hepatitis C virus (HCV), the combination of the direct-acting antiviral agent telaprevir, pegylated-interferon alfa (Peg-IFN), and ribavirin (RBV) significantly increases the chances of sustained virologic response (SVR) over treatment with Peg-IFN and RBV alone. If patients do not achieve SVR with telaprevir-based treatment, their viral population is often significantly enriched with telaprevir-resistant variants at the end of treatment. We sought to quantify the evolutionary dynamics of these post-treatment resistant variant populations.

Deep-sequencing analysis of the gene encoding the hepatitis C virus nonstructural 3-4A protease confirms a low prevalence of telaprevir-resistant variants at baseline and the end of the REALIZE study.

Background: Population sequencing (PS) has shown that telaprevir-resistant variants are not typically detectable at baseline (prevalence, ≤5% of patients), and most variants present at the time of treatment failure are no longer detectable at the end of the study.

Methods: To gain insight into the evolution of telaprevir-resistant variants, their baseline prevalence and persistence after treatment was investigated using a more sensitive, deep-sequencing (DS) technique in a large number of treatment-experienced patients from the REALIZE study who were infected with hepatitis C virus genotype 1.

Results: Before treatment initiation, telaprevir-resistant variants (T54A, T54S, or R155K in 1%-2% of the viral population) were detected by DS in a fraction (2%) of patients for whom PS failed to detect resistance; these variants were not necessarily detected at the time of treatment failure.

Virologic characterization of genotype 4 hepatitis C virus variants in patients treated with telaprevir.

Background: Study C210 was a Phase IIa, exploratory trial to assess the activity of telaprevir on hepatitis C virus (HCV) early viral kinetics in treatment-naïve patients infected with genotype 4 (G4) HCV.

Methods: Patients were randomized to receive peginterferon and ribavirin alone, telaprevir monotherapy (T arm), or telaprevir in combination with peginterferon/ribavirin (TPR arm) for 15 days, followed by a 46- or 48-week standard treatment phase. The current analysis aimed to characterize the genotype and phenotype of HCV G4 variants emerging during telaprevir treatment.

Patterns of viral load decline with telaprevir-based therapy in patients with genotype 1 chronic HCV infection.

Background: Telaprevir-based therapy is associated with rapid decline in HCV RNA, enabling the application of early futility rules.

Objectives: To familiarize physicians with this paradigm, a comprehensive analysis of the most frequent HCV viral load profiles observed during treatment with telaprevir/Peg-IFN/RBV in Phase III trials is provided.

Design: HCV RNA profiles were analyzed from 320 HCV genotype 1 treatment-naïve patients enrolled in the ADVANCE study, and 225 prior Peg-IFN/RBV treatment-experienced patients enrolled in the REALIZE study.

Telaprevir activity in treatment-naive patients infected hepatitis C virus genotype 4: a randomized trial.

Background: This partially blinded, randomized, phase 2a C210 study evaluated the antiviral activity of telaprevir-based regimens in treatment-naive patients with chronic hepatitis C virus (HCV) genotype 4 infection.

Methods: Twenty-four patients received telaprevir 750 mg every 8 hours for 15 days (T; n = 8), telaprevir in combination with pegylated interferon alfa-2a and ribavirin (Peg-IFN/RBV) for 15 days (TPR; n = 8), or Peg-IFN/RBV plus placebo for 15 days (PR; n = 8), followed by Peg-IFN/RBV for 46 or 48 weeks. The primary objective was to assess the effect of telaprevir on HCV RNA levels.

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

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.

Characterization of telaprevir treatment outcomes and resistance in patients with prior treatment failure: results from the REALIZE trial.

Unlabelled: In the Phase 3 REALIZE study, 662 genotype 1 hepatitis C virus (HCV)-infected patients with prior peginterferon/ribavirin treatment failure (including relapsers, partial, and null responders) were randomized to 12 weeks of telaprevir given immediately (T12/PR48) or following 4 weeks of peginterferon/ribavirin (lead-in T12/PR48), or 12 weeks of placebo (PR48), combined with a total of 48 weeks of peginterferon alfa-2a/ribavirin. Sustained virologic response (SVR) rates were 64% (T12/PR48), 66% (lead-in T12/PR48), and 17% (PR48). This analysis aimed to characterize treatment outcomes and viral variants emerging in telaprevir-treated patients not achieving SVR.

Hepatitis C viral evolution in genotype 1 treatment-naïve and treatment-experienced patients receiving telaprevir-based therapy in clinical trials.

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.