Darunavir
| Evidence Level: L5 | Predicted Indications: 4 |
Table of Contents
Darunavir: From HIV-1 Infection to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Darunavir is an HIV-1 protease inhibitor marketed in the US for HIV-1 infection. The TxGNN model predicts it may be effective for feline acquired immunodeficiency syndrome (FIV), but the evidence is very weak: 1 clinical trial and 0 publications, and the trial studied HIV-1 in humans, not FIV.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (the license records in the input carry no indication text, so this comes from darunavir’s established use) |
| Predicted New Indication | Feline acquired immunodeficiency syndrome |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L5 (the pack labels this L4, but it contains no FIV-specific preclinical or mechanism study) |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 (US authorizations, brand NDA and generic ANDAs combined) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the input. Darunavir is an HIV-1 protease inhibitor, and its efficacy in HIV-1 infection is well established. FIV is a related lentivirus, so the prediction is understandable at a superficial level.
However, FIV protease differs from HIV-1 protease in substrate specificity and inhibitor sensitivity, so activity against FIV cannot be assumed. The very high TxGNN score most likely reflects darunavir’s HIV-1 antiviral annotation spreading to related lentiviral disease nodes in the knowledge graph. It is not independent evidence for a feline indication.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02770508 | Phase 4 | Completed | 145 | Randomized open-label study of boosted darunavir plus lamivudine vs. boosted darunavir plus tenofovir/emtricitabine or tenofovir/lamivudine in treatment-naïve HIV-1 patients. It does not study FIV and only supports darunavir’s existing HIV-1 use (relevance grade C). |
Literature Evidence
Currently no related literature available.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA021976 | PREZISTA (Janssen Products LP) | Film-coated tablet | Not listed in the input |
| ANDA216168 | Darunavir (Camber Pharmaceuticals) | Film-coated tablet | Not listed in the input |
| ANDA214085 | Darunavir (Viona Pharmaceuticals) | Film-coated tablet | Not listed in the input |
| ANDA212493 | Darunavir (Amneal Pharmaceuticals NY) | Film-coated tablet | Not listed in the input |
Safety Considerations
Please refer to the package insert for safety information. No drug interaction records were found for this drug in the input.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on model output alone. No study tests darunavir against FIV, and the one trial found is a human HIV-1 study that only reflects the approved use. The other predicted indications are also weak. Simian immunodeficiency virus infection has only four non-human primate studies, where darunavir’s role is unconfirmed and would at most be part of a background regimen. The remaining two (a rare neurodevelopmental disorder and an obsolete hyperlipidemia term) have no evidence and no plausible mechanism.
To proceed, the following is needed:
- Package insert warnings and contraindications (currently blocking safety screening)
- Mechanism of action data for darunavir
- In vitro data on darunavir inhibition of FIV protease and FIV replication
- Veterinary-specific evidence and regulatory pathway assessment, since this would be a human drug used in cats
- Full-text check of whether darunavir was actually part of the regimens in the SIV studies
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.