Rilpivirine
| 證據等級: L5 | 預測適應症: 5 個 |
目錄
Rilpivirine: From HIV-1 Infection to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) originally developed for HIV-1 infection in humans. The TxGNN model's top-ranked prediction is feline acquired immunodeficiency syndrome — a veterinary disease caused by feline immunodeficiency virus (FIV), not a human indication — and this is currently supported by only 1 in vitro structural study and no clinical trials.
⚠️ Note on this candidate: The #1-ranked TxGNN prediction in this evidence pack targets a veterinary disease (cats), not a human condition. This is flagged as a likely low-value or off-target model output and is scored Hold in the evidence pack itself. Human-relevant candidates with much stronger evidence exist further down the same prediction list (see Conclusion).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (NNRTI; inferred from evidence pack literature/rationale — no formal Norway label text available) |
| Predicted New Indication | Feline acquired immunodeficiency syndrome (FIV infection in cats) |
| TxGNN Prediction Score | 99.97% |
| Evidence Level | L4 |
| Norway Market Status | ✗ Not marketed (未上市) |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in this evidence pack (original_moa: [Data Gap]). Based on information available in the supporting literature, rilpivirine is a diarylpyrimidine-class NNRTI that binds the HIV-1 reverse transcriptase (RT) enzyme, non-competitively blocking viral replication. Its efficacy in HIV-1 infection is well established, including in long-acting injectable combination form with cabotegravir.
The predicted new indication — feline immunodeficiency virus (FIV)-related syndrome — is mechanistically adjacent only in the broadest sense: FIV is also a lentivirus with a reverse transcriptase enzyme, so an NNRTI could in theory interfere with viral replication. However, FIV RT and HIV-1 RT are structurally distinct, and the single available study is a biochemical/structural comparison, not a functional antiviral efficacy study.
Per the evidence pack's own rationale: "僅有單一生化/結構比較研究，分析 NNRTI 對貓免疫缺陷病毒(FIV) RT 之結合特性；FIV RT 與 HIV-1 RT 結構差異顯著，交叉活性未經功能性驗證，屬獸醫學範疇而非人類藥物再利用標的。" In short, cross-species binding was studied structurally but never confirmed functionally, and the target species is not human — this is why the evidence pack itself assigns Evidence Level L4 and Decision Stage S0 / Hold.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 38031646 | 2023 | In vitro structural study | Journal of Veterinary Science | Compared biochemical/structural binding of NNRTIs (nevirapine, efavirenz, rilpivirine) against feline vs. human immunodeficiency virus reverse transcriptase, exploring theoretical potential of NNRTIs for FIV treatment in cats; no in vivo or clinical efficacy data reported. |
Norway Market Information
No authorization records found — rilpivirine is not currently marketed in Norway (total_licenses: 0, licenses: []).
Safety Considerations
Please refer to the package insert for safety information. (Key warnings, contraindications, and drug interaction data are all marked as data gaps in this evidence pack; DDI query returned no results.)
Conclusion and Next Steps
Decision: Hold
Rationale:
The top-ranked TxGNN prediction targets a veterinary condition (feline AIDS/FIV) rather than a human disease, is supported by only one preclinical structural-comparison paper with no functional or clinical validation, and is already self-scored L4 / Hold in the evidence pack. This candidate does not meet the bar for human drug repurposing evaluation.
To proceed, the following is needed:
- If pursuing this candidate specifically: functional antiviral efficacy data of rilpivirine against live FIV (in vitro or in vivo), and confirmation of veterinary regulatory pathway relevance (likely out of scope for a human repurposing program).
- Recommended alternative: re-scope this evaluation to rank 4 (
AIDS related complex, L2, Proceed with Guardrails) or rank 5 (congenital HIV— actually reflects CAB/RPV LA use in pregnant women with HIV, L2, Research Question), both of which have multiple Phase 3 trials and are within rilpivirine's actual human disease area. - Resolve blocking data gaps: DG001 (TFDA/Norway label warnings & contraindications — Blocking, required before any S1 safety review) and DG002 (formal MOA from DrugBank — High priority).
- Manually re-verify TxGNN disease-label mapping for rank 5 ("congenital human immunodeficiency virus"), as the underlying trial/literature evidence actually concerns maternal-fetal pharmacokinetics rather than a distinct congenital-HIV indication.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.