Darunavir
| 證據等級: L5 | 預測適應症: 4 個 |
目錄
Darunavir: From HIV-1 Infection to Simian Immunodeficiency Virus (SIV) Infection
One-Sentence Summary
Darunavir is a boosted HIV-1 protease inhibitor used as part of combination antiretroviral therapy (cART) for HIV/AIDS. The TxGNN model predicts it may be effective for Simian Immunodeficiency Virus (SIV) Infection — the primate-model correlate of HIV — but currently only 4 preclinical animal-model publications support this direction, none of which specifically test darunavir alone, and no clinical trials exist for this indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in evidence pack (drug is not marketed in Norway); known pharmacological classification is HIV-1 infection, treated as part of boosted cART regimens |
| Predicted New Indication | Simian Immunodeficiency Virus Infection |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L4 |
| Norway Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, darunavir is a member of the HIV-1 protease inhibitor (PI) class, its efficacy in HIV-1 infection (as part of boosted cART) has been proven, and mechanistically it may be applicable to SIV infection.
SIV is the retrovirus used to establish AIDS models in non-human primates and is genetically and structurally closely related to HIV-1, including a substantial degree of conservation in the Gag-Pol polyprotein processing pathway that PI-class drugs target. This cross-species mechanistic similarity is a well-established rationale for using HIV antiretrovirals, including PIs, in SIV-infected macaque research models.
However, it is important to note that the four supporting publications describe multi-drug cART regimens (some combined with adjunct agents such as the HDAC inhibitor SAHA or the gold compound auranofin) used in SIV/macaque reservoir and eradication research — darunavir (or PI-class drugs generally) appears only as one backbone component, not as the specific subject of efficacy testing. No study isolates or quantifies darunavir's individual contribution to SIV suppression.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 26150024 | 2016 | Animal Cohort | AIDS Res Hum Retroviruses | Compared two novel injectable coformulated cART regimens (PI-class backbone) for suppressing SIV replication in rhesus macaques |
| 25033210 | 2014 | Animal Cohort | PLoS One | Evaluated suppressive cART plus HDAC inhibitor SAHA on viral reservoirs in SIV-infected Chinese rhesus macaques |
| 22737073 | 2012 | Animal Cohort | PLoS Pathogens | Highly intensified multidrug ART achieved long-term viral suppression and reservoir restriction in SIVmac251-infected macaques |
| 21505294 | 2011 | Animal Cohort | AIDS (London) | Gold compound auranofin, added to ART, restricted the viral reservoir and delayed rebound after ART suspension in SIV-infected macaques |
Norway Market Information
Darunavir is currently not marketed in Norway; no authorization records are available in the evidence pack.
Safety Considerations
Please refer to the package insert for safety information.
Other TxGNN-Predicted Candidates (Reviewed, Not Recommended)
| Rank | Disease | Evidence Level | Reason for Hold |
|---|---|---|---|
| 2 | Feline acquired immunodeficiency syndrome | L4 | The single supporting trial (NCT02770508) is a human Phase 4 boosted-darunavir HIV regimen study, not a feline/FIV study — likely a disease-ontology mapping error in the knowledge graph; requires engineering review before further consideration |
| 3 | Neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter | L5 | No mechanistic rationale, no clinical or literature evidence — model score only |
| 4 | Obsolete familial combined hyperlipidemia | L5 | Mechanistically contradictory: darunavir (especially ritonavir-boosted regimens) is a known cause of dyslipidemia, making it a risk factor rather than a treatment; disease label is also flagged as obsolete |
Conclusion and Next Steps
Decision: Hold
Rationale: The only candidate reaching decision stage S1 (SIV infection) is supported solely by preclinical macaque studies in which darunavir is one component of multi-drug regimens, not the subject of dedicated efficacy testing — this is L4 evidence with no clinical trials. The remaining three candidates carry either a likely data/ontology error, no mechanistic support, or a mechanistically contraindicated relationship, and are all rated Hold.
To proceed, the following is needed:
- Darunavir-specific (monotherapy or defined-combination) efficacy data in SIV models, isolating its contribution from co-administered agents
- Resolution of the suspected disease-ontology mapping error for "feline acquired immunodeficiency syndrome" (rank 2) before any further evaluation
- TFDA/regulatory label data (warnings, contraindications, DDI) once available, to support S1 safety screening
- Confirmed original indication and MOA data from DrugBank or product labeling, since both are currently data gaps
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.