Glecaprevir
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Glecaprevir: From Chronic Hepatitis C to HIV Infectious Disease
One-Sentence Summary
Glecaprevir is an HCV NS3/4A protease inhibitor, originally used to treat chronic hepatitis C virus infection. The TxGNN model predicts it may be effective for HIV infectious disease, but the 7 clinical trials and 20 publications retrieved for this prediction all concern treating HCV (including in people who also have HIV), not HIV itself. The prediction is therefore best read as a research question rather than supported efficacy.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Chronic hepatitis C virus infection (the registered indication text is blank in the Singapore record, so this comes from the knowledge-graph indication data) |
| Predicted New Indication | HIV infectious disease |
| TxGNN Prediction Score | 99.87% |
| Evidence Level | L1 on the trial count alone, but the trials test HCV, not HIV. Direct evidence for HIV treatment is effectively L5 (model prediction only). |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Glecaprevir is known to be an HCV NS3/4A protease inhibitor, and it is used together with pibrentasvir (an NS5A inhibitor) as a fixed-dose combination for HCV.
Mechanistically, the prediction is hard to justify. Glecaprevir has no established direct antiretroviral activity. HIV is a retrovirus and does not have an NS3/4A-like protease target. The high TxGNN score most likely reflects network proximity between viral protease inhibitors and HIV-related targets in the knowledge graph.
The clinical link that does exist is about coinfection. Many people with HIV also have HCV, and the trials show glecaprevir/pibrentasvir can cure HCV in that group. That is a benefit for the HCV infection, not an HIV treatment effect.
The other nine predictions (hepatitis B, feline and simian immunodeficiency, hepatitis E, animal viral hepatitis, hepatitis A, Omsk hemorrhagic fever, Kyasanur forest disease, and a genetic neurodevelopmental disorder) all have even weaker support and are rated Hold.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02738138 | Phase 3 | Completed | 153 | EXPEDITION-2: efficacy and safety of glecaprevir/pibrentasvir in adults with HCV genotype 1-6 and HIV-1 coinfection (HCV endpoint) |
| NCT03235349 | Phase 3 | Completed | 160 | Asian adults with HCV and compensated cirrhosis, with or without HIV coinfection; supports HCV cure in coinfection only |
| NCT03222583 | Phase 3 | Completed | 546 | Randomized, placebo-controlled study in non-cirrhotic Asian adults with HCV, with or without HIV coinfection |
| NCT02634008 | Phase 3 | Completed | 83 | Pilot study of DAA regimens, including glecaprevir/pibrentasvir, in recently acquired HCV with or without HIV |
| NCT04042740 | Phase 2 | Completed | 45 | PURGE-C: 4-week glecaprevir/pibrentasvir for acute HCV, with or without HIV-1 coinfection |
| NCT03823911 | Phase 4 | Completed | 87 | Cardiovascular outcomes after HCV eradication in HIV/HCV-coinfected people compared with HIV-only controls |
| NCT07040319 | Phase 1/2 | Recruiting | 30 | Pharmacokinetics and safety of glecaprevir/pibrentasvir started in pregnancy in women with HCV, with or without HIV |
None of these trials has an HIV-directed efficacy endpoint.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37671831 | 2023 | Cohort | J Antimicrob Chemother | Real-world response to glecaprevir/pibrentasvir in HIV/HCV-coinfected patients |
| 41297677 | 2026 | Single-arm Phase IIIb trial | J Hepatol | 8-week glecaprevir/pibrentasvir in adults with acute HCV |
| 32754824 | 2020 | Cohort | Adv Ther | Real-world 8-week glecaprevir/pibrentasvir in treatment-naïve patients with compensated cirrhosis |
| 42578822 | 2026 | Cohort | Clin Infect Dis | Glecaprevir/pibrentasvir in pregnancy: 10 of 14 patients completed treatment, all with virologic response, no maternal or neonatal safety concerns |
| 39697370 | 2024 | Real-world study | Clin Exp Hepatol | Efficacy and safety of glecaprevir/pibrentasvir in HIV/HCV patients on bictegravir/emtricitabine/tenofovir alafenamide |
| 31284039 | 2019 | Systematic review and meta-analysis | Int J Antimicrob Agents | 13 studies, 3,082 patients; pooled SVR12 of 97.8% in HCV |
| 34664197 | 2021 | Case report | Clin J Gastroenterol | Successful HCV genotype 4a treatment in a hemophilia patient coinfected with HIV |
| 30499343 | 2019 | Review | Future Microbiol | Glecaprevir/pibrentasvir for chronic HCV |
| 29595065 | 2018 | Review | Expert Opin Pharmacother | Protease inhibitor therapy for HCV, noting frequent HIV coinfection |
| 38293756 | 2024 | Systematic review and meta-analysis | Liver Int | Efficacy and safety of DAAs, including glecaprevir/pibrentasvir, in children and adolescents with HCV |
All of these address HCV. None shows an effect on HIV itself.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15603P | MAVIRET FILM-COATED TABLET 100MG/40MG | Film-coated tablet (oral) | Indication text not recorded in the registration data |
Safety Considerations
- Drug Interactions: 57 interactions were identified. Those shown below are the Major-level ones in the retrieved data:
- Rosuvastatin (Major)
- Simvastatin (Major)
- Edoxaban (Major)
- Moderate-level interactions include dexamethasone, omeprazole, esomeprazole, cobicistat, apixaban, betrixaban, deferasirox, lusutrombopag, metreleptin, naldemedine, revefenacin, griseofulvin and troglitazone.
- Minor-level interactions include fidaxomicin, naloxegol, prucalopride and indacaterol.
- The cobicistat interaction deserves attention in any HIV setting, since cobicistat is a common antiretroviral booster.
Please refer to the package insert for warnings and contraindications, which were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: Although the trial count would formally reach L1, every trial and publication tests glecaprevir/pibrentasvir for HCV, including in people with HIV coinfection. None tests HIV treatment. Glecaprevir has no plausible direct anti-HIV mechanism, so the high TxGNN score appears to be a network-based artifact. Its value in people with HIV is curing their HCV, which is already its approved use.
To proceed, the following is needed:
- In vitro evidence of anti-HIV activity, or a plausible mechanism, before any clinical exploration
- Mechanism of action data (MOA)
- Package insert warnings and contraindications from the Singapore regulator
- Drug interaction review for antiretroviral regimens, especially cobicistat-boosted ones and statins
- Consideration of whether the better framing is "HCV treatment in HIV/HCV coinfection", which is already within the existing indication
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.