Integrated Efficacy and Safety of Glecaprevir/Pibrentasvir to Treat HCV Genotype 1-6 Infection in Patients Without Cirrhosis Including HIV Co-Infection
Bibliographic record
Abstract
Introduction: Glecaprevir, an NS3/4A protease inhibitor (developed by AbbVie and Enanta) and pibrentasvir (NS5A inhibitor), collectively G/P, is a once-daily, pangenotypic, direct-acting antiviral (DAA) regimen shown to be efficacious in the treatment of all major genotypes (GT) of hepatitis C virus (HCV). Here, we present an integrated efficacy and safety analysis of 8-, 12-, and 16-week durations of G/P in non-cirrhotic HCV GT 1-6 patients, including those with HIV co-infection. Methods: Data were pooled from the SURVEYOR-I and -II and ENDURANCE-1, -2, -3, and -4, and EXPEDITION-2 and -4 studies. Patients were either treatment-naïve or treatment-experienced with interferon (IFN), pegIFN ± ribavirin (RBV), or sofosbuvir (SOF) + RBV ± pegIFN. Patients with experience to a DAA other than SOF were excluded. Patients with GT1, 2, 4, 5, and 6 infection received 8 or 12 weeks of G/P regardless of treatment history, whereas treatment-experienced GT3-infected patients received 16 weeks of G/P. Efficacy was evaluated as the rate of sustained virologic response (HCV RNA < lower limit of quantification) at 12 weeks post-treatment (SVR12) using a modified intent-to-treat analysis excluding those not achieving SVR for reasons other than virologic failure. Safety was assessed in all patients. Results: In total, 2063 chronic HCV patients without cirrhosis were included in the analysis comprised of 55% (1135/2063) males, 79% (1639/2063) white race, 24% (494/2063) treatment experienced, and 8% (170/2063) HIV co-infected. SVR12 rates are shown in Figure 1 according to treatment duration and genotype. In the modified intent-to-treat (mITT) population, overall SVR12 rates were 99.1% for the 8-week (943/952) and 99.6% for the 12-week groups (1060/1064). The SVR12 rate was 95% (21/22) for treatment-experienced GT3 patients receiving 16-weeks of G/P. In patients with HIV co-infection, 100% (169/169) of patients achieved SVR12. Overall, G/P was well-tolerated with 1 (< 0.1%) DAA-related serious adverse events and 10 (0.5%) adverse events leading to treatment discontinuation.Figure: mITT Analysis of Integrated Efficacy for 8-, 12-, and 16-week G/P treatment.Conclusion: G/P for 8, 12, and 16 weeks in chronic HCV GT1-6 infected patients without cirrhosis was well-tolerated and achieved high SVR12 rates. These data suggest that the majority of patients without cirrhosis can be treated for 8 weeks with G/P.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".