Doravirine

證據等級: L5

預測適應症: 3 個

Doravirine: From HIV-1 Infection to Feline Acquired Immunodeficiency Syndrome

One-Sentence Summary

Doravirine is an HIV-1-specific non-nucleoside reverse transcriptase inhibitor (NNRTI) approved in the United States and European Union for HIV-1 treatment in adults, though not yet marketed in Taiwan. The TxGNN model predicts it may be effective for Feline Acquired Immunodeficiency Syndrome (Feline AIDS), however there are 0 clinical trials and 0 publications directly supporting this direction. All three top-ranked predictions carry an Evidence Level of L5 and a “Hold” recommendation, raising concern that these scores reflect knowledge graph topology rather than true repurposing signals.

Quick Overview

Item	Content
Original Indication	HIV-1 infection (approved in US/EU; not marketed in Taiwan)
Predicted New Indication	Feline Acquired Immunodeficiency Syndrome
TxGNN Prediction Score	99.93%
Evidence Level	L5
Taiwan Market Status	✗ Not Marketed
Number of Product Licenses	0
Recommended Decision	Hold

Why Is This Prediction Reasonable?

Detailed mechanism of action data is not available in the current Evidence Pack. Based on known information, Doravirine is an HIV-1-specific NNRTI that binds to the non-catalytic allosteric binding pocket (NNIBP) of the HIV-1 reverse transcriptase (RT) enzyme, blocking viral replication without competing with the nucleotide substrate.

Feline Acquired Immunodeficiency Syndrome is caused by Feline Immunodeficiency Virus (FIV), which — like HIV-1 — belongs to the lentivirus family. This shared family classification is almost certainly why the TxGNN knowledge graph model assigned a high prediction score: the graph’s taxonomic proximity between HIV and FIV nodes creates apparent similarity. However, the structural similarity ends at the family level. FIV reverse transcriptase has a significantly different NNIBP configuration compared to HIV-1 RT, with key residue differences at positions critical for NNRTI binding (e.g., K101, Y181, Y188). Published literature consistently reports that HIV-1 NNRTIs — including earlier-generation drugs like nevirapine and efavirenz — have little to no measurable activity against FIV.

This prediction is most likely a false association generated by knowledge graph traversal rather than a genuine mechanistic repurposing opportunity. It should be treated as noise unless new experimental data demonstrates FIV-RT inhibition by doravirine.

Clinical Trial Evidence

Currently no related clinical trials registered for Doravirine in Feline Acquired Immunodeficiency Syndrome.

Literature Evidence

Currently no related literature available directly linking Doravirine to Feline Acquired Immunodeficiency Syndrome.

Taiwan Market Information

Doravirine currently has no approved product licenses in Taiwan (0 registrations). It is approved in the United States as Pifeltro® (MSD/Merck) and in the European Union for HIV-1 treatment in adults, but has not entered the Taiwan market as of the data cutoff date (2026-04-04).

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Hold

Rationale: All three TxGNN top-ranked predictions — Feline Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus infection, and a rare neurodevelopmental disorder with ataxic gait — are entirely unsupported by clinical or published literature evidence (Evidence Level L5 across the board). The leading prediction (Feline AIDS) is a veterinary disease, and the mechanistic basis for Doravirine’s efficacy against FIV is structurally implausible given the divergence of NNIBP residues between HIV-1 and FIV reverse transcriptases. These predictions appear to be knowledge graph artifacts rather than actionable repurposing signals.

To proceed, the following is needed:

MOA confirmation: Retrieve full mechanism of action profile from DrugBank API (DB12301) to enable proper mechanistic analysis
Safety data: Obtain TFDA package insert (or US/EU SmPC) to populate key warnings, contraindications, and drug interaction data — currently all blocking gaps
Target reassessment: Re-evaluate TxGNN output focused on human viral or immune-mediated diseases where Doravirine’s NNRTI mechanism may be more plausibly applicable (e.g., hepatitis B co-infection, HTLV-associated conditions, or immune reconstitution contexts)
In vitro validation gate: Before advancing any non-HIV indication, require FIV-RT or SIV-RT inhibition data (IC₅₀ assay) as a minimum biological proof-of-concept
Taiwan registration pathway: If a credible human indication is identified, assess regulatory pathway for Taiwan market entry given current zero-license status
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.