Raltegravir
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
Raltegravir: From HIV-1 Infection to Feline Acquired Immunodeficiency Syndrome
One-Sentence Summary
Raltegravir is a well-established HIV-1 integrase strand transfer inhibitor (INSTI); the evidence pack itself does not confirm its original licensed indication or mechanism of action. The TxGNN model’s top prediction is Feline Acquired Immunodeficiency Syndrome (FIV) with a score of 99.78%, but the underlying evidence — two Phase 3 clinical trials in human HIV-1 patients — has been explicitly flagged by the source analysis as an unrelated, text-matching false positive, not genuine cross-species evidence. No literature or trials support this prediction directly; the recommendation is Hold.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not provided in evidence pack (original_indications field empty; Raltegravir is generically known as an HIV-1 integrase inhibitor, but this was not captured in the pack) |
| Predicted New Indication | Feline Acquired Immunodeficiency Syndrome |
| TxGNN Prediction Score | 99.78% |
| Evidence Level | L5 |
| UK Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the evidence pack (flagged as a Blocking-severity data gap for TFDA/MHRA warnings and a High-severity gap for MOA). Based on generally established pharmacological knowledge, Raltegravir belongs to the integrase strand transfer inhibitor (INSTI) class, used in combination antiretroviral therapy for HIV-1 infection.
The TxGNN model’s top-ranked prediction — Feline Acquired Immunodeficiency Syndrome (FIV) — has a superficial mechanistic rationale: FIV is a lentivirus, as is HIV, and both depend on an integrase enzyme to insert viral DNA into the host genome. However, the two clinical trials attached as “supporting evidence” (NCT01231516, NCT01227824) are in fact head-to-head Phase 3 trials comparing Raltegravir with Dolutegravir in human HIV-1-infected adults, not FIV-infected cats. Both trials were graded C (low relevance) in the source analysis, with the explicit conclusion that this is a knowledge-graph embedding artefact caused by textual similarity between “immunodeficiency syndrome” terms, rather than real cross-species evidence. No feline-specific trial, veterinary literature, or pharmacokinetic data for cats is present anywhere in the evidence pack.
Two lower-ranked predictions from the same run are worth noting for context, though outside the scope of this report’s primary indication: Simian Immunodeficiency Virus (SIV) infection (rank 2, L3, “Research Question” stage) is genuinely supported by multiple non-human primate studies — but this reflects Raltegravir’s established role as a research tool in SIV/macaque models of HIV, not a new human therapeutic indication. A rare neurodevelopmental disorder (rank 3, L5) has no supporting trials or literature at all and rests purely on a speculative interferonopathy hypothesis. None of the three top predictions constitute an actionable new human indication at this time.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01231516 | Phase 3 | Completed | 724 | Dolutegravir vs Raltegravir in antiretroviral-experienced, integrase-inhibitor-naïve human HIV-1 adults — not related to feline disease; graded C relevance (false-positive text match) |
| NCT01227824 | Phase 3 | Completed | 828 | Dolutegravir vs Raltegravir in antiretroviral-naïve human HIV-1 adults — not related to feline disease; graded C relevance (false-positive text match) |
Note: Neither trial provides genuine support for the predicted indication (FIV). They are included here only because they were linked by the TxGNN evidence pipeline; both are confirmed unrelated to feline disease.
Literature Evidence
Currently no related literature available.
UK Market Information
No marketing authorisations are recorded in the evidence pack (total_licenses: 0, licenses: []; market status: Not marketed).
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: The top-ranked prediction (Feline Acquired Immunodeficiency Syndrome) is not a viable human repurposing candidate — it is a companion-animal disease, and the source analysis has already identified the supporting trials as a text-matching false positive with no genuine mechanistic or clinical linkage. No literature or veterinary evidence exists to support this direction. The next-best prediction (SIV infection) is a non-human primate research model application rather than a new human indication, and the third (a rare neurodevelopmental disorder) has zero supporting evidence.
To proceed, the following is needed:
- TFDA/MHRA SmPC warnings and contraindications (currently a Blocking data gap)
- Confirmed mechanism of action and original licensed indication for Raltegravir (currently a High-severity data gap)
- Re-run of the TxGNN prediction pipeline with species/organism filtering to exclude non-human disease terms from the human drug repurposing candidate list
- If SIV-related research applications are of interest, a separate evaluation scoped explicitly as a non-human primate research tool, not a clinical repurposing candidate
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.