Glecaprevir

Evidence Level: L5

Predicted Indications: 10

Glecaprevir

Pharmacist Assessment Report

Glecaprevir: HIV infectious disease

One-Sentence Summary

Glecaprevir is a hepatitis C virus (HCV) NS3/4A protease inhibitor, marketed in Australia in a fixed-dose tablet with pibrentasvir (Maviret). The TxGNN model predicts it may be relevant to HIV infectious disease, but the studies retrieved treat hepatitis C in people who also have HIV, not HIV itself. Evidence level is L5: 7 clinical trials and 21 publications were retrieved, but none directly studies HIV infection as the target disease.

Quick Overview

Item	Content
Original Indication	Not recorded in the local data
Predicted New Indication	HIV infectious disease
TxGNN Prediction Score	0.9987
Evidence Level	L5
Australia Market Status	Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data
Number of PBS Items	1 (valid: 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 inhibit the HCV NS3/4A protease, and it has no established direct anti-HIV activity.

The high TxGNN score most likely reflects the close relationship between HIV and HCV: the two infections share patient populations, and there are well-documented drug interactions between HCV antivirals and HIV antiretrovirals. The retrieved trials and papers involve HIV/HCV co-infection, where glecaprevir/pibrentasvir treats the hepatitis C component. This is better understood as use in a co-infected population than as true repurposing against HIV. The prediction should be treated as a research question, not a treatment signal.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT02738138	Phase 3	Completed	153	EXPEDITION-2: glecaprevir/pibrentasvir (ABT-493/ABT-530) in HCV genotype 1–6 with HIV-1 co-infection; the endpoint is HCV outcome
NCT03222583	Phase 3	Completed	546	Placebo-controlled study in non-cirrhotic Asian adults with HCV, with or without HIV co-infection
NCT03235349	Phase 3	Completed	160	Open-label study in Asian adults with HCV and compensated cirrhosis, with or without HIV co-infection
NCT02634008	Phase 3	Completed	83	Pilot of DAA regimens, including glecaprevir/pibrentasvir, in recently acquired HCV with or without HIV; the regimen is largely paritaprevir-based
NCT04042740	Phase 2	Completed	45	PURGE-C: 4-week glecaprevir/pibrentasvir in acute HCV, with or without HIV-1 co-infection
NCT03823911	Phase 4	Completed	87	Cardiovascular risk after HCV eradication in HCV mono-infected and HIV/HCV co-infected people
NCT07040319	Phase 1/2	Recruiting	30	Pharmacokinetics and safety of glecaprevir/pibrentasvir started in pregnancy, with or without HIV

All of these trials measure HCV or related outcomes. None tests glecaprevir as a treatment for HIV infection itself.

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
39697370	2024	Observational	Clin Exp Hepatol	Effectiveness of glecaprevir/pibrentasvir in HIV/HCV patients on bictegravir/emtricitabine/tenofovir alafenamide
31504702	2020	Pharmacology	J Infect Dis	Drug interactions of glecaprevir/pibrentasvir with HIV antiretrovirals
31284039	2019	Meta-analysis	Int J Antimicrob Agents	Systematic review of 13 studies (3,082 patients); overall SVR12 97.8% in HCV
41297677	2026	Single-arm Phase IIIb	J Hepatol	8-week glecaprevir/pibrentasvir in acute HCV
32754824	2020	Cohort	Adv Ther	Real-world 8-week regimen in treatment-naive patients with compensated cirrhosis
31114957	2019	Review	Clin Pharmacokinet	Pharmacokinetic and pharmacodynamic considerations for HCV therapy
30499343	2019	Review	Future Microbiol	Overview of glecaprevir/pibrentasvir for chronic HCV
29595065	2018	Review	Expert Opin Pharmacother	Protease inhibitor therapy for HCV, noting HIV coinfection rates
38367631	2024	Review	Lancet Gastroenterol Hepatol	Global registration and reimbursement of HCV direct-acting antivirals

The literature concerns HCV treatment, including in people with HIV. It does not show anti-HIV activity.

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 11332K	Maviret	Tablet containing 100 mg glecaprevir with 40 mg pibrentasvir	Not stated in the data compiled for this report

Safety Considerations

Drug Interactions (57 interactions recorded; selected examples):

Major: rosuvastatin, simvastatin, edoxaban
Moderate: dexamethasone, esomeprazole, omeprazole, apixaban, betrixaban, cobicistat, deferasirox, metreleptin, naldemedine, troglitazone, lusutrombopag, revefenacin, griseofulvin
Minor: fidaxomicin, naloxegol, prucalopride, indacaterol

Because HIV antiretrovirals are frequently co-prescribed, interaction checking is particularly important (see PMID 31504702). Please refer to the TGA-approved Product Information (PI) for warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: Glecaprevir has no established anti-HIV mechanism, and every trial and publication retrieved addresses hepatitis C, including in people with HIV co-infection, rather than HIV infection itself. The evidence level is therefore L5, and the high score most likely reflects the HIV–HCV relationship rather than an HIV-directed effect.

To proceed, the following is needed:

In vitro evidence of anti-HIV activity, as no such data are currently available
Detailed mechanism of action data
Clarification of whether the intended value lies in treating HCV in co-infected people (an existing use) rather than in treating HIV
Review of the PI for safety and antiretroviral interaction guidance

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.