Doravirine
| 證據等級: L5 | 預測適應症: 3 個 |
目錄
Doravirine: From HIV-1 Infection to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI), a class developed to treat HIV-1 infection in humans. TxGNN's top-ranked prediction is feline acquired immunodeficiency syndrome (FIV) — a veterinary disease of cats — with 0 clinical trials and 0 publications currently supporting this direction. This prediction should be treated as a low-confidence computational signal rather than an actionable repurposing candidate.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (based on known drug classification; not present in evidence pack) |
| Predicted New Indication | Feline acquired immunodeficiency syndrome (FIV) |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L5 |
| Germany Market Status | 未上市 (Not marketed) |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the evidence pack. Based on known pharmacology, doravirine is an NNRTI approved for human HIV-1 infection (marketed as Pifeltro, and combined with lamivudine/tenofovir disoproxil fumarate as Delstrigo). It works by binding non-competitively to HIV-1 reverse transcriptase, blocking conversion of viral RNA to DNA.
Feline immunodeficiency virus (FIV) is a lentivirus related to but structurally distinct from HIV-1; it causes an AIDS-like syndrome in cats. While both viruses share the lentivirus family and rely on reverse transcriptase, NNRTIs such as doravirine are generally not cross-reactive against FIV reverse transcriptase due to sequence and binding-pocket differences. The TxGNN score likely reflects a broad "immunodeficiency virus / RT inhibitor" association embedded in the knowledge graph rather than a validated pharmacological mechanism. Critically, FIV is a veterinary indication in cats, not a human clinical indication — making this prediction non-actionable for human drug repurposing regardless of mechanistic plausibility.
The two other candidates in this evidence pack were already flagged as low value: simian immunodeficiency virus infection (rank 2) is supported only by a review article about islatravir — a different drug with a different mechanism (NRTTI, not NNRTI) — so it does not constitute evidence for doravirine; and the rare neurodevelopmental disorder (rank 3) has no plausible mechanistic link to reverse transcriptase inhibition and is most likely a knowledge-graph artifact.
Clinical Trial Evidence
Currently no related clinical trials registered
Literature Evidence
Currently no related literature available
Germany Market Information
Doravirine is not currently marketed in Germany (0 authorizations on record); no BfArM license data is available in this evidence pack.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: No clinical trials or literature support any of the three TxGNN-predicted indications. The top-ranked prediction (FIV) is a veterinary disease with no established mechanistic cross-reactivity to doravirine's NNRTI activity, and the drug is not currently marketed in Germany.
To proceed, the following is needed:
- TFDA/BfArM 官方仿單警語與禁忌資料（DG001，Blocking，目前無法進入安全性初評）
- Doravirine 完整作用機轉 (MOA) 官方資料來源（DG002）
- 若欲評估人類可行之老藥新用方向，需針對人類相關疾病重新查詢 TxGNN 預測結果——目前三項候選皆非可行之人類臨床標的
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.