Darunavir
| Evidence Level: L4 | 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 (data confirmed via the drug’s repurposing rationale; formal MOA record is a data gap), most widely known for treating human HIV/AIDS in combination antiretroviral regimens. The TxGNN model’s top-ranked prediction is Feline Acquired Immunodeficiency Syndrome (FIV), with a 99.97% prediction score, but the single supporting clinical trial is judged to be a poor match and this candidate is likely a knowledge-graph ontology artefact (FIV vs. HIV node confusion) rather than a genuine repurposing signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (known pharmacological class information; not documented in this evidence pack — see Data Gaps) |
| Predicted New Indication | Feline Acquired Immunodeficiency Syndrome |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L4 |
| UK Market Status | Not Marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, a formal mechanism-of-action record is not available for this evidence pack. Based on the information present, Darunavir is an HIV-1 protease inhibitor, typically used as part of ritonavir- or cobicistat-boosted combination antiretroviral therapy (cART) for HIV-1 infection.
The top-ranked predicted indication, Feline Acquired Immunodeficiency Syndrome (FIV), is a veterinary disease caused by feline immunodeficiency virus, a lentivirus related to but distinct from HIV. The only supporting clinical trial identified (NCT02770508) is in fact a human Phase 4 study comparing darunavir-based cART regimens in HIV-1-infected adults — it has no connection to feline disease. This mismatch has been flagged (relevance grade C) as most likely reflecting an ontology/node-mapping error in the knowledge graph (FIV vs. HIV), rather than genuine pharmacological evidence. On that basis, this specific prediction should not be interpreted as a credible repurposing opportunity.
A biologically more plausible — though still non-human — related prediction is Simian Immunodeficiency Virus (SIV) infection (rank 2, also 99.97%, L3/Research Question). SIV is the standard macaque model virus for HIV/AIDS research, and darunavir-containing cART regimens are used in this model to study viral reservoirs. This reflects translational/animal-model research use rather than a new human clinical indication.
Clinical Trial Evidence
(from the top-ranked prediction, Feline Acquired Immunodeficiency Syndrome)
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT02770508 | Phase 4 | Completed | 145 | Compared boosted darunavir + lamivudine vs. boosted darunavir + emtricitabine/tenofovir or lamivudine/tenofovir in treatment-naïve human HIV-1-infected adults. Note: this trial is in humans with HIV-1, not cats with FIV — it does not support the stated feline indication and is very likely a knowledge-graph mismatch. |
Literature Evidence
Currently no related literature is registered for the top-ranked (Feline AIDS) prediction.
For completeness, the closely related rank-2 prediction (Simian Immunodeficiency Virus infection) is supported by 4 PubMed records (PMIDs 26150024, 25033210, 22737073, 21505294), all animal-model cohort studies (Tier 3) evaluating darunavir-containing cART in SIV-infected macaques — these describe translational research use, not an approved or emerging human indication.
Other Predicted Indications (Not Recommended)
This evidence pack contains four TxGNN candidates for Darunavir, none of which currently support progression:
| Rank | Predicted Indication | Score | Evidence Level | Recommendation | Note |
|---|---|---|---|---|---|
| 1 | Feline Acquired Immunodeficiency Syndrome | 99.97% | L4 | Hold | Likely FIV/HIV ontology mismatch; sole trial is a human HIV study |
| 2 | Simian Immunodeficiency Virus infection | 99.97% | L3 | Research Question | Animal-model translational research only, not a human indication |
| 3 | Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter | 99.97% | L5 | Hold | Rare monogenic syndrome; no mechanistic link, no supporting trials/literature |
| 4 | Obsolete familial combined hyperlipidemia | 99.19% | L5 | Hold | Mechanistically contradictory — boosted PIs are known to cause dyslipidaemia as an adverse effect, not treat it; disease node is itself marked obsolete |
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Conclusion and Next Steps
Decision: Hold
Rationale: None of the four TxGNN-predicted indications for Darunavir currently constitute a credible human repurposing candidate. The top-ranked prediction (feline AIDS) appears to be a knowledge-graph artefact rather than genuine evidence, the second-ranked prediction (SIV) reflects animal-model research rather than a new clinical indication, and the remaining two candidates (L5) have no supporting mechanism, trials, or literature — one of them is mechanistically implausible. Darunavir also has no current UK marketing authorisation recorded in this evidence pack.
To proceed, the following is needed:
- Resolve the FIV/HIV node-mapping issue in the knowledge graph before this candidate can be re-scored
- Confirm formal mechanism-of-action (MOA) documentation (currently a data gap)
- Obtain manufacturer/SmPC safety data (warnings, contraindications, DDI) — currently a blocking data gap for any safety pre-assessment
- Clarify UK market status/licensing pathway, since no marketing authorisations are currently on record
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.