Darunavir
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Darunavir: From HIV Infection to Simian Immunodeficiency Virus Infection
One-Sentence Summary
Darunavir is an HIV-1 protease inhibitor, originally used to treat HIV infection and AIDS. The TxGNN model predicts it may be effective for simian immunodeficiency virus (SIV) infection, but there are no registered clinical trials and only 4 publications, all macaque studies of combination antiretroviral therapy (not darunavir alone). This is an animal-model indication that largely restates the original indication, so it is not a true repurposing opportunity.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV infection, AIDS (the Singapore licence records contain no approved indication text; this comes from the knowledge graph) |
| Predicted New Indication | Simian immunodeficiency virus infection |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 5 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, darunavir is an HIV-1 protease inhibitor. Its efficacy in HIV infection is established, and mechanistically it may be applicable to SIV infection.
SIV is the non-human primate counterpart of HIV, and the two viruses have related proteases, so the mechanistic rationale is strong. However, the retrieved publications describe macaque studies of combination ART, latency-reversing agents and viral reservoir restriction. Their titles do not show that darunavir was tested as a single agent.
SIV infection is an animal-model indication with no human clinical value beyond the existing HIV indication. It is not a new therapeutic opportunity.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25033210 | 2014 | Preclinical (non-human primate) | PloS one | Suppressive combination ART plus the histone deacetylase inhibitor SAHA in SIV-infected Chinese rhesus macaques, as a model of viral reservoirs |
| 26150024 | 2016 | Preclinical (non-human primate) | AIDS Res Hum Retroviruses | Comparison of two coformulated injectable combination ART regimens in SIVmac239-infected rhesus macaques |
| 22737073 | 2012 | Preclinical (non-human primate) | PLoS Pathogens | Highly intensified multidrug ART produced long-term viral suppression and restricted the viral reservoir in a simian AIDS model |
| 21505294 | 2011 | Preclinical (non-human primate) | AIDS | Gold compound auranofin restricted the viral reservoir in the monkey AIDS model and helped contain viral load after ART suspension |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13853P | PREZISTA™ Tablet 75 mg | Film-coated tablet | Not stated in the licence record |
| SIN13854P | PREZISTA™ Tablet 150 mg | Film-coated tablet | Not stated in the licence record |
| SIN13855P | PREZISTA™ Tablet 400 mg | Film-coated tablet | Not stated in the licence record |
| SIN13856P | PREZISTA™ Tablet 600 mg | Film-coated tablet | Not stated in the licence record |
| SIN14595P | PREZISTA™ Tablet 800 mg | Film-coated tablet | Not stated in the licence record |
Safety Considerations
- Disease-related cautions (from the knowledge graph, not label text): Darunavir is linked to contraindication or caution signals in liver failure, liver disease, cirrhosis, chronic hepatitis B and C infection, gallbladder disease, diabetes mellitus, hyperglycaemia, diabetic ketoacidosis, hypertriglyceridaemia, and haemophilia.
- Drug Interactions: 100 interactions were found. The sample reviewed includes one Major interaction, with cisapride. The other interactions in the sample are Moderate, including:
- Antidiabetic agents: acarbose, albiglutide, alogliptin, metformin, pioglitazone, canagliflozin, dapagliflozin, saxagliptin, chlorpropamide, acetohexamide
- Corticosteroids: hydrocortisone, dexamethasone, betamethasone, budesonide, triamcinolone
- Others: aprepitant, clarithromycin
Please refer to the package insert for the official warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The SIV prediction is supported only by preclinical macaque studies of combination ART, with no darunavir-specific evidence and no registered trials. It is an animal-model indication that restates the existing HIV indication, so it offers no new human therapeutic value.
To proceed, the following is needed:
- Mechanism of action data for darunavir
- Package insert warnings and contraindications, which are needed before any safety screening
- Evidence that darunavir alone was tested in SIV models, if this indication is pursued for research purposes
Other predicted indications: Congenital HIV (rank 6) has the most human-relevant support, with pharmacokinetic and pregnancy-safety literature. It is a variant of the approved HIV indication rather than a new disease, and could be treated as a research question. The remaining predictions (feline AIDS, a neurodevelopmental disorder, obsolete familial combined hyperlipidaemia, AIDS-related complex, and benign prostate and reproductive neoplasms) have no supporting evidence or only overlap with the existing HIV indication.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.