Raltegravir
| 證據等級: L5 | 預測適應症: 3 個 |
目錄
Raltegravir: From HIV-1 Infection to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Raltegravir is an HIV-1 integrase strand transfer inhibitor (INSTI), originally studied and used for treating HIV-1 infection in humans. The TxGNN model predicts it may be effective for Feline Acquired Immunodeficiency Syndrome, but the 2 clinical trials currently linked to this prediction are Phase 3 studies conducted in human HIV-1 patients, not in cats, and no literature specific to the feline indication was found.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HIV-1 infection (inferred from linked trial descriptions; no formal original_indications or market-label text was provided in the evidence pack) |
| Predicted New Indication | Feline Acquired Immunodeficiency Syndrome |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L4 (the linked trials are mechanistic/analogous — human HIV-1 studies — not direct feline-indication studies) |
| 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 (marked as a High-severity data gap). Based on the clinical trial evidence linked to this candidate, raltegravir is described as an integrase strand transfer inhibitor (INSTI) used in combination antiretroviral regimens for HIV-1 infected patients — this is stated directly in the trial descriptions (e.g., "raltegravir (RAL) 400 mg twice daily" as background therapy for HIV-1 infected adults).
Mechanistically, the rationale for extending raltegravir to Feline Acquired Immunodeficiency Syndrome would rest on the fact that both HIV (in humans) and FIV-associated feline AIDS are caused by lentiviruses that depend on a viral integrase enzyme to insert proviral DNA into the host genome. An integrase inhibitor effective against HIV-1 integrase could, in principle, be evaluated against the analogous feline lentiviral integrase.
However, this rationale remains theoretical at this stage: the two Phase 3 trials attached as "evidence" for this indication (NCT01231516, NCT01227824) are actually human HIV-1 studies comparing raltegravir to dolutegravir — they do not involve cats or FIV. No feline-specific trial or publication was identified. The prediction should therefore be read as a cross-species mechanistic hypothesis rather than one currently backed by direct experimental or clinical data in the target species.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01231516 | Phase 3 | Completed | 724 | Human HIV-1 study: dolutegravir 50mg QD vs. raltegravir 400mg BID, both with investigator-selected background regimen, in integrase-inhibitor-naïve, ART-experienced adults. Not a feline study. |
| NCT01227824 | Phase 3 | Completed | 828 | Human HIV-1 study: dolutegravir 50mg QD vs. raltegravir 400mg BID with fixed-dose dual NRTI therapy in ART-naïve adults. Not a feline study. |
Note: These trials establish raltegravir's antiviral efficacy against HIV-1 in humans but do not directly test the predicted feline indication.
Literature Evidence
Currently no related literature available.
Norway Market Information
Raltegravir is not currently marketed in Norway; no market authorizations are on record in the evidence pack.
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The predicted indication (Feline Acquired Immunodeficiency Syndrome) targets a non-human species, and the only clinical trials currently linked to this candidate are human HIV-1 studies rather than feline-specific studies — direct relevance has not yet been established. Combined with a Blocking data gap on regulatory safety information and a High-severity gap on mechanism of action, there is insufficient basis to advance this candidate at this time.
To proceed, the following is needed:
- Verification of whether any preclinical or veterinary (FIV) in vitro/in vivo data exist for raltegravir, separate from the human HIV-1 trial evidence currently attached
- Package insert / SPC data to close the Blocking safety data gap (key warnings, contraindications, DDI)
- Detailed mechanism of action documentation from DrugBank
- Clarification of relevance grading for the linked trials and literature (currently marked "pending" in the evidence pack) to confirm whether the KG-derived indication mapping is a genuine signal or an ontology/text-matching artifact (e.g., "acquired immunodeficiency syndrome" string overlap between human and feline terms)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.